Academic Journal

Intracellular Staphylococcus aureus triggers isolate-specific host transcriptional responses alongside TNF-R1 regulated cell fate decisions.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Intracellular Staphylococcus aureus triggers isolate-specific host transcriptional responses alongside TNF-R1 regulated cell fate decisions.
Συγγραφείς: Walter A; Department of Infection Prevention and Infectious Diseases, University Hospital of Regensburg, University of Regensburg, Regensburg, 93053, Germany., Bischler T; Core Unit Systems Medicine, University of Würzburg, Würzburg, Germany., Jungblut M; Rudolf-Virchow-Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany., Breitsprecher LF; Center of Cellular Nanoanalytics Osnabrück, Integrated Bioimaging Facility, University of Osnabrück, Osnabrück, Germany., Vilotic F; Department of Infection Prevention and Infectious Diseases, University Hospital of Regensburg, University of Regensburg, Regensburg, 93053, Germany., Beck J; Department of Infection Prevention and Infectious Diseases, University Hospital of Regensburg, University of Regensburg, Regensburg, 93053, Germany., Hofmann L; Institute for Molecular and Cellular Anatomy, University of Regensburg, Regensburg, Germany., Schäfer N; Department of Orthopedic Surgery, Experimental Orthopedics, Center for Medical Biotechnology (ZMB), University of Regensburg, Regensburg, Germany., Ziesmann T; Institute for Immunology, University Medical Center of the Johannes-Gutenberg University, Mainz, Germany., Franzkoch R; Center of Cellular Nanoanalytics Osnabrück, Integrated Bioimaging Facility, University of Osnabrück, Osnabrück, Germany., Härteis S; Institute for Molecular and Cellular Anatomy, University of Regensburg, Regensburg, Germany., Gadjalova I; Institute for Clinical Chemistry and Pathobiochemistry, School of Medicine, Technical University of Munich, Munich, Germany.; TranslaTUM, Center for Translational Cancer Research, Technical University Munich, Munich, Germany., Distler U; Institute for Immunology, University Medical Center of the Johannes-Gutenberg University, Mainz, Germany., Beliu G; Rudolf-Virchow-Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany.; Regensburg Center for Ultrafast Nanoscopy, University of Regensburg, Regensburg, Germany., Psathaki OE; Center of Cellular Nanoanalytics Osnabrück, Integrated Bioimaging Facility, University of Osnabrück, Osnabrück, Germany., Hensel M; Center of Cellular Nanoanalytics Osnabrück, Integrated Bioimaging Facility, University of Osnabrück, Osnabrück, Germany.; Division of Microbiology, University of Osnabrück, Osnabrück, Germany., Schneider-Brachert W; Department of Infection Prevention and Infectious Diseases, University Hospital of Regensburg, University of Regensburg, Regensburg, 93053, Germany., Gräfenhan T; Core Unit Systems Medicine, University of Würzburg, Würzburg, Germany., Stempfl T; Center of Excellence for Fluorescent Bioanalytics (KFB), University of Regensburg, Regensburg, Germany., Kieninger B; Department of Infection Prevention and Infectious Diseases, University Hospital of Regensburg, University of Regensburg, Regensburg, 93053, Germany., Mühlen S; Department of Molecular Immunology, Ruhr-University Bochum, Bochum, Germany., Alt V; Department of Trauma Surgery, University Hospital Regensburg, Regensburg, Germany., Mannala GK; Department of Trauma Surgery, University Hospital Regensburg, Regensburg, Germany., Fritsch J; Department of Infection Prevention and Infectious Diseases, University Hospital of Regensburg, University of Regensburg, Regensburg, 93053, Germany. Juergen.Fritsch@ukr.de.
Πηγή: Cell communication and signaling : CCS [Cell Commun Signal] 2026 Sep 28; Vol. 24 (1). Date of Electronic Publication: 2026 Sep 28.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: BioMed Central Country of Publication: England NLM ID: 101170464 Publication Model: Electronic Cited Medium: Internet ISSN: 1478-811X (Electronic) Linking ISSN: 1478811X NLM ISO Abbreviation: Cell Commun Signal Subsets: MEDLINE
Imprint Name(s): Original Publication: [London] : BioMed Central, c2003-
Ιατρικοί όροι (MeSH): Staphylococcus aureus*/isolation & purification , Staphylococcus aureus*/physiology , Receptors, Tumor Necrosis Factor, Type I*/metabolism , Receptors, Tumor Necrosis Factor, Type I*/genetics , Host-Pathogen Interactions*/genetics , Intracellular Space*/microbiology , Transcription, Genetic*, Monocytes/microbiology ; Monocytes/metabolism ; Humans ; U937 Cells ; Signal Transduction ; Apoptosis
Περίληψη: Background: Staphylococcus aureus (S. aureus) is an increasingly recognized intracellular pathogen, yet infection outcomes vary with bacterial isolate and host cell type. Many mechanisms underlying these differences remain poorly understood. This study investigated how distinct intracellular S. aureus isolates influence host signaling programs and infection outcomes by modulating cell death pathways and TNF-R1 dependent regulation of host cell fates across different human cell lines.
Methods: The intracellular localization of four S. aureus isolates was analyzed via transmission electron microscopy (TEM), structured illumination microscopy (SIM), serial block-face scanning electron microscopy (SBF-SEM), and imaging flow cytometry. The transcriptional reprogramming of infected U937 monocytes was examined via mRNA sequencing. Infection outcomes and early TNF-R1 surface expression were characterized and compared with those of A549 and SaOS-2 cell lines employing flow cytometry and Western blot analysis, characterizing host cell death mechanisms in both wild-type and TNF-R1‒deficient backgrounds.
Results: All S. aureus isolates localized to the endo-lysosomal and cytosolic compartments but were also frequently detected in nucleo-proximal regions. In U937 monocytes, infection induced a conserved stress signature alongside isolate‑specific transcriptional programs divergently affecting inflammation, metabolism, and cell fate, which was markedly attenuated in response to the chronic‑infection isolate EDCC 5464. Similarly, cell death outcomes were isolate‑ and cell type-dependent, involved caspase activation consistent with intrinsic and extrinsic apoptosis signaling, and caspase-1 activation at distinct temporal dynamics. TNF‑R1 loss initially delayed but later increased later isolate-independent cytotoxicity. Higher TNF-R1 surface expression was triggered in U937 monocytes by all viable isolates, but only by EDCC 5464 in SaOS-2 and A549 cells. Viability of the latter was only marginally influenced by isolate or TNF-R1 loss.
Conclusions: These results highlight the multilayered determinants governing intracellular S. aureus survival, host cell susceptibility, and noncanonical intracellular localization that warrants further investigation. The TNF/TNF-R1 axis appears to critically influence regulated host defenses during early infection stages in a tissue-specific manner, though its mechanistic contribution remains to be fully elucidated. Together with distinct isolate-driven gene expression profiles of U937 monocytes, infection risks under TNF-targeted therapies and the contribution of S. aureus heterogeneity should be considered in the design of future host-directed treatment strategies.
(© 2026. The Author(s).)
Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
References: Adv Appl Microbiol. 2020;112:105-141. (PMID: 32762866)
J Immunol Methods. 2012 Oct 31;384(1-2):111-7. (PMID: 22867743)
Autophagy. 2021 Apr;17(4):888-902. (PMID: 32174246)
PLoS One. 2011 Apr 22;6(4):e18899. (PMID: 21526122)
Cell Death Differ. 2025 Jul;32(7):1336-1352. (PMID: 40021897)
J Cell Biol. 2005 Aug 1;170(3):477-85. (PMID: 16061696)
Bioinformatics. 2014 Apr 1;30(7):923-30. (PMID: 24227677)
Clin Microbiol Rev. 2020 Jun 10;33(3):. (PMID: 32522746)
Cancers (Basel). 2021 May 21;13(11):. (PMID: 34063813)
Nucleic Acids Res. 2016 Aug 19;44(14):6614-24. (PMID: 27342282)
Antibiotics (Basel). 2023 Sep 14;12(9):. (PMID: 37760742)
Methods Mol Biol. 2015;1228:15-23. (PMID: 25311118)
BMC Microbiol. 2019 May 9;19(1):91. (PMID: 31072343)
Nat Rev Microbiol. 2011 Mar;9(3):215-22. (PMID: 21297670)
EMBO Mol Med. 2018 Oct;10(10):. (PMID: 30171089)
J Immunol. 2000 Apr 1;164(7):3713-22. (PMID: 10725730)
Science. 2000 Jun 30;288(5475):2351-4. (PMID: 10875917)
Front Cell Dev Biol. 2025 Feb 27;13:1534281. (PMID: 40083666)
Scand J Immunol. 2005 Jun;61(6):536-44. (PMID: 15963048)
Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):10794-9. (PMID: 23754403)
Med Microbiol Immunol. 2019 Oct;208(5):585-607. (PMID: 30483863)
Nat Commun. 2025 Dec 10;16(1):10907. (PMID: 41372130)
J Exp Med. 2018 Mar 05;215(3):985-997. (PMID: 29436394)
Bioinformatics. 2015 Nov 15;31(22):3691-3. (PMID: 26198102)
Front Microbiol. 2020 Jul 15;11:1643. (PMID: 32760383)
Cell Commun Signal. 2019 Aug 5;17(1):90. (PMID: 31382980)
Microbiol Res. 2017 Dec;205:19-24. (PMID: 28942840)
Eur J Immunol. 2020 Aug;50(8):1174-1186. (PMID: 32250445)
Cell Death Differ. 2004 May;11(5):550-63. (PMID: 14739942)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
Eur Cell Mater. 2014 Oct 23;28:258-68. (PMID: 25340805)
PLoS One. 2019 Apr 1;14(4):e0214586. (PMID: 30934018)
EMBO J. 1999 Jun 1;18(11):3034-43. (PMID: 10357816)
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6721-5. (PMID: 8692885)
Genome Announc. 2017 Feb 23;5(8):. (PMID: 28232428)
Adv Exp Med Biol. 2025;1481:241-292. (PMID: 41004085)
PLoS Pathog. 2015 Apr 29;11(4):e1004870. (PMID: 25923704)
Nucleic Acids Res. 2023 Jul 5;51(W1):W207-W212. (PMID: 37144459)
Int J Med Microbiol. 2018 Jul;308(5):505-513. (PMID: 29739668)
Cell Microbiol. 2003 Oct;5(10):729-41. (PMID: 12969378)
Infect Immun. 2000 Sep;68(9):5385-92. (PMID: 10948168)
Front Immunol. 2023 Mar 31;14:1046374. (PMID: 37063823)
Int J Med Microbiol. 2004 Sep;294(2-3):195-202. (PMID: 15493830)
J Clin Invest. 2006 Nov;116(11):2901-13. (PMID: 17024246)
PLoS One. 2010 Nov 15;5(11):e13984. (PMID: 21085593)
Virulence. 2025 Dec;16(1):2553789. (PMID: 40888369)
PLoS Negl Trop Dis. 2017 Jan 3;11(1):e0005241. (PMID: 28045926)
J Transl Med. 2025 Jan 15;23(1):71. (PMID: 39815286)
J Cell Sci. 2002 Jul 1;115(Pt 13):2757-70. (PMID: 12077366)
mBio. 2018 Jul 17;9(4):. (PMID: 30018109)
Transl Oncol. 2021 Jan;14(1):100922. (PMID: 33137543)
Infect Immun. 2015 Oct 26;84(1):241-53. (PMID: 26502911)
Cell Microbiol. 2017 Dec;19(12):. (PMID: 28873268)
Front Pharmacol. 2023 Jul 24;14:1169327. (PMID: 37554981)
Cell Prolif. 2026 Aug;59(8):e70196. (PMID: 41815017)
Appl Environ Microbiol. 2020 Aug 18;86(17):. (PMID: 32591386)
Infect Immun. 2015 Sep;83(9):3445-57. (PMID: 26099586)
Microbiology (Reading). 2008 Oct;154(Pt 10):3033-3041. (PMID: 18832309)
Infect Immun. 1996 Aug;64(8):2974-9. (PMID: 8757823)
mBio. 2022 Oct 26;13(5):e0231622. (PMID: 36102512)
Signal Transduct Target Ther. 2021 Mar 29;6(1):128. (PMID: 33776057)
Oncotarget. 2016 Nov 15;7(46):75774-75789. (PMID: 27716614)
Curr Opin Immunol. 2019 Oct;60:103-110. (PMID: 31228759)
Trends Cell Biol. 2015 Jun;25(6):339-46. (PMID: 25680230)
PLoS Pathog. 2021 Sep 2;17(9):e1009874. (PMID: 34473800)
J Innate Immun. 2010;2(6):560-75. (PMID: 20587998)
Clin Immunol. 2022 May;238:109018. (PMID: 35460903)
Front Cell Infect Microbiol. 2012 Apr 24;2:43. (PMID: 22919634)
Genome Res. 2014 May;24(5):839-49. (PMID: 24717264)
Nat Methods. 2020 Dec;17(12):1229-1236. (PMID: 33257825)
Front Cell Infect Microbiol. 2022 Apr 07;12:854242. (PMID: 35531332)
Front Cell Infect Microbiol. 2025 Oct 30;15:1644443. (PMID: 41245260)
Ann Rheum Dis. 2014 Sep;73(9):1673-6. (PMID: 23740236)
Immunobiology. 2020 Mar;225(2):151887. (PMID: 31822434)
PLoS Pathog. 2018 Jun 14;14(6):e1007112. (PMID: 29902272)
Cell Microbiol. 2014 Apr;16(4):451-65. (PMID: 24164701)
Nat Protoc. 2019 Feb;14(2):482-517. (PMID: 30664679)
Cell Host Microbe. 2010 Jan 21;7(1):38-49. (PMID: 20114027)
Cell. 2003 Jul 25;114(2):181-90. (PMID: 12887920)
Autoimmun Rev. 2012 Dec;12(2):225-9. (PMID: 22796281)
Int J Med Microbiol. 2014 Mar;304(2):170-6. (PMID: 24365645)
PLoS One. 2013;8(1):e53589. (PMID: 23349721)
Bone Joint Res. 2022 May;11(5):327-341. (PMID: 35604422)
Cell Microbiol. 2005 Aug;7(8):1087-97. (PMID: 16008576)
Clin Microbiol Infect. 2026 Jun;32(6):886-888. (PMID: 41856403)
Infect Immun. 1999 Aug;67(8):4201-7. (PMID: 10417192)
J Proteomics. 2020 Jul 15;223:103821. (PMID: 32417293)
Immunology. 1996 Apr;87(4):544-50. (PMID: 8675207)
Cell Death Differ. 2003 Nov;10(11):1260-72. (PMID: 12894214)
Nat Protoc. 2016 Apr;11(4):795-812. (PMID: 27010757)
Pathog Glob Health. 2024 May;118(3):209-231. (PMID: 38006316)
PLoS One. 2009 Oct 14;4(10):e7446. (PMID: 19826485)
Cold Spring Harb Perspect Med. 2012 Dec 01;2(12):a010272. (PMID: 23209181)
BMC Microbiol. 2010 Nov 02;10:275. (PMID: 21044323)
Curr Rheumatol Rep. 2008 Oct;10(5):383-9. (PMID: 18817643)
Mol Immunol. 2008 Apr;45(7):2087-96. (PMID: 18022234)
Nature. 2009 Aug 27;460(7259):1159-63. (PMID: 19641494)
Trop Med Int Health. 1998 Mar;3(3):242-8. (PMID: 9593364)
J Infect Dis. 2024 Dec 16;230(6):1488-1500. (PMID: 38805184)
Cell Microbiol. 2016 Nov;18(11):1583-1595. (PMID: 27062399)
Traffic. 2019 Mar;20(3):246-258. (PMID: 30569578)
Immunol Res. 2019 Jun;67(2-3):241-260. (PMID: 31290001)
PLoS Pathog. 2016 Sep 15;12(9):e1005857. (PMID: 27632173)
Mol Cell Proteomics. 2019 May;18(5):892-908. (PMID: 30808728)
Front Pharmacol. 2021 Nov 01;12:746396. (PMID: 34790122)
Bioinformatics. 2013 Jan 1;29(1):15-21. (PMID: 23104886)
Nat Commun. 2023 Jul 18;14(1):4290. (PMID: 37463962)
BMC Bioinformatics. 2020 Apr 10;21(1):139. (PMID: 32272889)
Traffic. 2013 Mar;14(3):321-36. (PMID: 23231467)
Infect Immun. 2003 May;71(5):2716-23. (PMID: 12704146)
Nat Methods. 2020 Jan;17(1):41-44. (PMID: 31768060)
Appl Environ Microbiol. 2025 Aug 20;91(8):e0021125. (PMID: 40679283)
Nat Commun. 2022 Nov 22;13(1):7174. (PMID: 36418309)
J Bacteriol. 1991 Oct;173(20):6313-20. (PMID: 1717437)
Sci Adv. 2023 Jun 16;9(24):eadf8748. (PMID: 37327341)
J Neuroinflammation. 2024 Jul 23;21(1):179. (PMID: 39044282)
Front Immunol. 2020 Nov 11;11:565545. (PMID: 33262756)
PLoS One. 2017 Aug 9;12(8):e0182415. (PMID: 28793310)
Infect Immun. 2014 Oct;82(10):4144-53. (PMID: 25047846)
Nat Methods. 2009 May;6(5):359-62. (PMID: 19377485)
Proc Natl Acad Sci U S A. 2022 Aug 2;119(31):e2123017119. (PMID: 35881802)
PLoS Pathog. 2015 Jun 12;11(6):e1004970. (PMID: 26069969)
Nucleic Acids Res. 2017 Jan 4;45(D1):D1107-D1111. (PMID: 27899654)
Sci Rep. 2021 Mar 16;11(1):6037. (PMID: 33727596)
Am J Physiol Cell Physiol. 2025 Nov 1;329(5):C1672-C1680. (PMID: 41117409)
Front Cell Infect Microbiol. 2019 Mar 07;9:57. (PMID: 30899700)
Science. 1999 Jan 22;283(5401):543-6. (PMID: 9915703)
Physiol Rev. 2019 Jan 1;99(1):115-160. (PMID: 30354964)
Inflamm Bowel Dis. 2023 Mar 1;29(3):339-348. (PMID: 35776552)
Cell Microbiol. 2016 Apr;18(4):514-35. (PMID: 26408990)
Clin Microbiol Infect. 2026 Jun;32(6):951-958. (PMID: 41690515)
Sci Rep. 2023 Jan 21;13(1):1188. (PMID: 36681703)
Int J Med Microbiol. 2018 Aug;308(6):607-624. (PMID: 29217333)
Clin Microbiol Infect. 2016 Sep;22(9):799-809. (PMID: 27393124)
Infect Immun. 1970 Oct;2(4):387-91. (PMID: 16557850)
Nat Methods. 2012 Jul;9(7):671-5. (PMID: 22930834)
Clin Infect Dis. 2001 Jun 1;32(11):1643-7. (PMID: 11340539)
PLoS One. 2015 Feb 26;10(2):e0117713. (PMID: 25719526)
J Bacteriol. 2002 Oct;184(19):5457-67. (PMID: 12218034)
Cell Microbiol. 2019 Mar;21(3):e12997. (PMID: 30576050)
PLoS Pathog. 2021 Jan 21;17(1):e1009184. (PMID: 33476322)
Cell Res. 2015 Jun;25(6):707-25. (PMID: 25952668)
J Infect Dis. 2012 Oct;206(8):1185-93. (PMID: 22872735)
Virchows Arch B Cell Pathol. 1973;14(1):35-45. (PMID: 4355691)
Thorac Cancer. 2019 Mar;10(3):437-444. (PMID: 30628200)
Bioinformatics. 2014 Jul 15;30(14):2068-9. (PMID: 24642063)
J Infect Dis. 1992 Jul;166(1):58-64. (PMID: 1607709)
Front Cell Infect Microbiol. 2026 Jun 15;16:1840752. (PMID: 42376318)
J Biol Chem. 2007 Jan 26;282(4):2695-706. (PMID: 17135247)
PLoS Pathog. 2015 Apr 16;11(4):e1004820. (PMID: 25880560)
J Clin Invest. 2024 Oct 1;134(19):. (PMID: 39352382)
Bone Marrow Transplant. 1992 May;9(5):369-76. (PMID: 1617321)
Infect Immun. 1998 Jan;66(1):336-42. (PMID: 9423876)
J Transl Med. 2019 Jul 2;17(1):215. (PMID: 31266509)
Grant Information: 318346496, 446605368 Deutsche Forschungsgemeinschaft; 422048538, 467522186 Deutsche Forschungsgemeinschaft; 547933897 Deutsche Forschungsgemeinschaft
Contributed Indexing: Keywords: Staphylococcus aureus; Apoptosis; Host cell death; Host response; Host‒pathogen interactions; Intracellular infection; Perinuclear; TNF receptor 1; TNF-α; Transcriptomics
Local Abstract: [plain-language-summary] The bacterium Staphylococcus aureus (S. aureus) often lives harmlessly in humans but can cause severe or recurrent infections when the skin barrier is broken or when the immune system is weakened. A major reason for its persistence is its ability to hide inside human cells, where it is shielded from immune attacks and antibiotics. To effectively target such bacteria, it is crucial to understand that infections vary depending on both the bacterial strain and the infected tissue type. Many reasons behind these differences are still puzzling. We explored how different types of S. aureus (collected from different disease types) change how different human cells respond to infection. We focused on how each strain influences the way immune cells adjust their gene activity during infection, and how a receptor called TNF‑R1 is involved in managing cell death responses.Bacteria are found in compartments meant to destroy them but frequently also in close association to the cell nucleus, an unexpected location that requires further investigation. All strains triggered a similar stress response but also distinct patterns differentially influencing inflammation, metabolism, and cell survival. A strain linked to chronic infection caused weaker responses, suggesting greater ability to remain undetected. The immune cells had greater presence of TNF-R1 on their surface when infected, and when they lacked this receptor entirely, they initially survived longer but later showed greater damage, indicating its key role in infection control. In lung and bone cells, these effects were less pronounced.In conclusion, S. aureus uses various survival strategies that have heterogeneous impact on different host tissues. Some bacteria localized to unexpected compartments close to the cell’s control center inside all analyzed human cell types. Importantly, while the exact mechanisms are not yet clear, TNF-R1 influences host infection responses in the studied immune cells, highlighting that the interaction of bacterial programs and critical host factors must be carefully considered when developing targeted treatments.
Substance Nomenclature: 0 (Receptors, Tumor Necrosis Factor, Type I)
Entry Date(s): Date Created: 20260929 Date Completed: 20260930 Latest Revision: 20261001
Update Code: 20261001
PubMed Central ID: PMC13621601
DOI: 10.1186/s12964-026-03246-8
PMID: 42811321
Βάση Δεδομένων: MEDLINE
FullText Text:
  Availability: 0
CustomLinks:
  – Url: https://resolver.ebsco.com/c/fiv2js/result?sid=EBSCO:cmedm&genre=article&issn=1478811X&ISBN=&volume=24&issue=1&date=20260928&spage=&pages=&title=Cell communication and signaling : CCS&atitle=Intracellular%20Staphylococcus%20aureus%20triggers%20isolate-specific%20host%20transcriptional%20responses%20alongside%20TNF-R1%20regulated%20cell%20fate%20decisions.&aulast=Walter%20A&id=DOI:10.1186/s12964-026-03246-8
    Name: Full Text Finder (for New FTF UI) (ns324271)
    Category: fullText
    Text: Full Text Finder
    MouseOverText: Full Text Finder
Header DbId: cmedm
DbLabel: MEDLINE
An: 42811321
AccessLevel: 3
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Intracellular Staphylococcus aureus triggers isolate-specific host transcriptional responses alongside TNF-R1 regulated cell fate decisions.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AU" term="%22Walter+A%22">Walter A</searchLink>; Department of Infection Prevention and Infectious Diseases, University Hospital of Regensburg, University of Regensburg, Regensburg, 93053, Germany.<br /><searchLink fieldCode="AU" term="%22Bischler+T%22">Bischler T</searchLink>; Core Unit Systems Medicine, University of Würzburg, Würzburg, Germany.<br /><searchLink fieldCode="AU" term="%22Jungblut+M%22">Jungblut M</searchLink>; Rudolf-Virchow-Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany.<br /><searchLink fieldCode="AU" term="%22Breitsprecher+LF%22">Breitsprecher LF</searchLink>; Center of Cellular Nanoanalytics Osnabrück, Integrated Bioimaging Facility, University of Osnabrück, Osnabrück, Germany.<br /><searchLink fieldCode="AU" term="%22Vilotic+F%22">Vilotic F</searchLink>; Department of Infection Prevention and Infectious Diseases, University Hospital of Regensburg, University of Regensburg, Regensburg, 93053, Germany.<br /><searchLink fieldCode="AU" term="%22Beck+J%22">Beck J</searchLink>; Department of Infection Prevention and Infectious Diseases, University Hospital of Regensburg, University of Regensburg, Regensburg, 93053, Germany.<br /><searchLink fieldCode="AU" term="%22Hofmann+L%22">Hofmann L</searchLink>; Institute for Molecular and Cellular Anatomy, University of Regensburg, Regensburg, Germany.<br /><searchLink fieldCode="AU" term="%22Schäfer+N%22">Schäfer N</searchLink>; Department of Orthopedic Surgery, Experimental Orthopedics, Center for Medical Biotechnology (ZMB), University of Regensburg, Regensburg, Germany.<br /><searchLink fieldCode="AU" term="%22Ziesmann+T%22">Ziesmann T</searchLink>; Institute for Immunology, University Medical Center of the Johannes-Gutenberg University, Mainz, Germany.<br /><searchLink fieldCode="AU" term="%22Franzkoch+R%22">Franzkoch R</searchLink>; Center of Cellular Nanoanalytics Osnabrück, Integrated Bioimaging Facility, University of Osnabrück, Osnabrück, Germany.<br /><searchLink fieldCode="AU" term="%22Härteis+S%22">Härteis S</searchLink>; Institute for Molecular and Cellular Anatomy, University of Regensburg, Regensburg, Germany.<br /><searchLink fieldCode="AU" term="%22Gadjalova+I%22">Gadjalova I</searchLink>; Institute for Clinical Chemistry and Pathobiochemistry, School of Medicine, Technical University of Munich, Munich, Germany.; TranslaTUM, Center for Translational Cancer Research, Technical University Munich, Munich, Germany.<br /><searchLink fieldCode="AU" term="%22Distler+U%22">Distler U</searchLink>; Institute for Immunology, University Medical Center of the Johannes-Gutenberg University, Mainz, Germany.<br /><searchLink fieldCode="AU" term="%22Beliu+G%22">Beliu G</searchLink>; Rudolf-Virchow-Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany.; Regensburg Center for Ultrafast Nanoscopy, University of Regensburg, Regensburg, Germany.<br /><searchLink fieldCode="AU" term="%22Psathaki+OE%22">Psathaki OE</searchLink>; Center of Cellular Nanoanalytics Osnabrück, Integrated Bioimaging Facility, University of Osnabrück, Osnabrück, Germany.<br /><searchLink fieldCode="AU" term="%22Hensel+M%22">Hensel M</searchLink>; Center of Cellular Nanoanalytics Osnabrück, Integrated Bioimaging Facility, University of Osnabrück, Osnabrück, Germany.; Division of Microbiology, University of Osnabrück, Osnabrück, Germany.<br /><searchLink fieldCode="AU" term="%22Schneider-Brachert+W%22">Schneider-Brachert W</searchLink>; Department of Infection Prevention and Infectious Diseases, University Hospital of Regensburg, University of Regensburg, Regensburg, 93053, Germany.<br /><searchLink fieldCode="AU" term="%22Gräfenhan+T%22">Gräfenhan T</searchLink>; Core Unit Systems Medicine, University of Würzburg, Würzburg, Germany.<br /><searchLink fieldCode="AU" term="%22Stempfl+T%22">Stempfl T</searchLink>; Center of Excellence for Fluorescent Bioanalytics (KFB), University of Regensburg, Regensburg, Germany.<br /><searchLink fieldCode="AU" term="%22Kieninger+B%22">Kieninger B</searchLink>; Department of Infection Prevention and Infectious Diseases, University Hospital of Regensburg, University of Regensburg, Regensburg, 93053, Germany.<br /><searchLink fieldCode="AU" term="%22Mühlen+S%22">Mühlen S</searchLink>; Department of Molecular Immunology, Ruhr-University Bochum, Bochum, Germany.<br /><searchLink fieldCode="AU" term="%22Alt+V%22">Alt V</searchLink>; Department of Trauma Surgery, University Hospital Regensburg, Regensburg, Germany.<br /><searchLink fieldCode="AU" term="%22Mannala+GK%22">Mannala GK</searchLink>; Department of Trauma Surgery, University Hospital Regensburg, Regensburg, Germany.<br /><searchLink fieldCode="AU" term="%22Fritsch+J%22">Fritsch J</searchLink>; Department of Infection Prevention and Infectious Diseases, University Hospital of Regensburg, University of Regensburg, Regensburg, 93053, Germany. Juergen.Fritsch@ukr.de.
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22101170464%22">Cell communication and signaling : CCS</searchLink> [Cell Commun Signal] 2026 Sep 28; Vol. 24 (1). <i>Date of Electronic Publication: </i>2026 Sep 28.
– Name: TypePub
  Label: Publication Type
  Group: TypPub
  Data: Journal Article
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: TitleSource
  Label: Journal Info
  Group: Src
  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22BioMed+Central%22">BioMed Central </searchLink><i>Country of Publication: </i>England <i>NLM ID: </i>101170464 <i>Publication Model: </i>Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1478-811X (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%221478811X%22">1478811X </searchLink><i>NLM ISO Abbreviation: </i>Cell Commun Signal <i>Subsets: </i>MEDLINE
– Name: PublisherInfo
  Label: Imprint Name(s)
  Group: PubInfo
  Data: <i>Original Publication</i>: [London] : BioMed Central, c2003-
– Name: SubjectMESH
  Label: MeSH Terms
  Group: Su
  Data: <searchLink fieldCode="MM" term="%22Staphylococcus+aureus%22">Staphylococcus aureus*</searchLink>/<searchLink fieldCode="MM" term="%22Staphylococcus+aureus+isolation+%26+purification%22">isolation & purification</searchLink> <br /><searchLink fieldCode="MM" term="%22Staphylococcus+aureus%22">Staphylococcus aureus*</searchLink>/<searchLink fieldCode="MM" term="%22Staphylococcus+aureus+physiology%22">physiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Receptors%2C+Tumor+Necrosis+Factor%2C+Type+I%22">Receptors, Tumor Necrosis Factor, Type I*</searchLink>/<searchLink fieldCode="MM" term="%22Receptors%2C+Tumor+Necrosis+Factor%2C+Type+I+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Receptors%2C+Tumor+Necrosis+Factor%2C+Type+I%22">Receptors, Tumor Necrosis Factor, Type I*</searchLink>/<searchLink fieldCode="MM" term="%22Receptors%2C+Tumor+Necrosis+Factor%2C+Type+I+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Host-Pathogen+Interactions%22">Host-Pathogen Interactions*</searchLink>/<searchLink fieldCode="MM" term="%22Host-Pathogen+Interactions+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Intracellular+Space%22">Intracellular Space*</searchLink>/<searchLink fieldCode="MM" term="%22Intracellular+Space+microbiology%22">microbiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Transcription%2C+Genetic%22">Transcription, Genetic*</searchLink><br /><searchLink fieldCode="MH" term="%22Monocytes%22">Monocytes</searchLink>/<searchLink fieldCode="MH" term="%22Monocytes+microbiology%22">microbiology</searchLink> ; <searchLink fieldCode="MH" term="%22Monocytes%22">Monocytes</searchLink>/<searchLink fieldCode="MH" term="%22Monocytes+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22U937+Cells%22">U937 Cells</searchLink> ; <searchLink fieldCode="MH" term="%22Signal+Transduction%22">Signal Transduction</searchLink> ; <searchLink fieldCode="MH" term="%22Apoptosis%22">Apoptosis</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: Staphylococcus aureus (S. aureus) is an increasingly recognized intracellular pathogen, yet infection outcomes vary with bacterial isolate and host cell type. Many mechanisms underlying these differences remain poorly understood. This study investigated how distinct intracellular S. aureus isolates influence host signaling programs and infection outcomes by modulating cell death pathways and TNF-R1 dependent regulation of host cell fates across different human cell lines.<br />Methods: The intracellular localization of four S. aureus isolates was analyzed via transmission electron microscopy (TEM), structured illumination microscopy (SIM), serial block-face scanning electron microscopy (SBF-SEM), and imaging flow cytometry. The transcriptional reprogramming of infected U937 monocytes was examined via mRNA sequencing. Infection outcomes and early TNF-R1 surface expression were characterized and compared with those of A549 and SaOS-2 cell lines employing flow cytometry and Western blot analysis, characterizing host cell death mechanisms in both wild-type and TNF-R1‒deficient backgrounds.<br />Results: All S. aureus isolates localized to the endo-lysosomal and cytosolic compartments but were also frequently detected in nucleo-proximal regions. In U937 monocytes, infection induced a conserved stress signature alongside isolate‑specific transcriptional programs divergently affecting inflammation, metabolism, and cell fate, which was markedly attenuated in response to the chronic‑infection isolate EDCC 5464. Similarly, cell death outcomes were isolate‑ and cell type-dependent, involved caspase activation consistent with intrinsic and extrinsic apoptosis signaling, and caspase-1 activation at distinct temporal dynamics. TNF‑R1 loss initially delayed but later increased later isolate-independent cytotoxicity. Higher TNF-R1 surface expression was triggered in U937 monocytes by all viable isolates, but only by EDCC 5464 in SaOS-2 and A549 cells. Viability of the latter was only marginally influenced by isolate or TNF-R1 loss.<br />Conclusions: These results highlight the multilayered determinants governing intracellular S. aureus survival, host cell susceptibility, and noncanonical intracellular localization that warrants further investigation. The TNF/TNF-R1 axis appears to critically influence regulated host defenses during early infection stages in a tissue-specific manner, though its mechanistic contribution remains to be fully elucidated. Together with distinct isolate-driven gene expression profiles of U937 monocytes, infection risks under TNF-targeted therapies and the contribution of S. aureus heterogeneity should be considered in the design of future host-directed treatment strategies.<br /> (© 2026. The Author(s).)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Declarations. Competing interests: The authors declare no competing interests.
– Name: Ref
  Label: References
  Group: RefInfo
  Data: Adv Appl Microbiol. 2020;112:105-141. (PMID: <searchLink fieldCode="PM" term="%2232762866%22">32762866)</searchLink><br />J Immunol Methods. 2012 Oct 31;384(1-2):111-7. (PMID: <searchLink fieldCode="PM" term="%2222867743%22">22867743)</searchLink><br />Autophagy. 2021 Apr;17(4):888-902. (PMID: <searchLink fieldCode="PM" term="%2232174246%22">32174246)</searchLink><br />PLoS One. 2011 Apr 22;6(4):e18899. (PMID: <searchLink fieldCode="PM" term="%2221526122%22">21526122)</searchLink><br />Cell Death Differ. 2025 Jul;32(7):1336-1352. (PMID: <searchLink fieldCode="PM" term="%2240021897%22">40021897)</searchLink><br />J Cell Biol. 2005 Aug 1;170(3):477-85. (PMID: <searchLink fieldCode="PM" term="%2216061696%22">16061696)</searchLink><br />Bioinformatics. 2014 Apr 1;30(7):923-30. (PMID: <searchLink fieldCode="PM" term="%2224227677%22">24227677)</searchLink><br />Clin Microbiol Rev. 2020 Jun 10;33(3):. (PMID: <searchLink fieldCode="PM" term="%2232522746%22">32522746)</searchLink><br />Cancers (Basel). 2021 May 21;13(11):. (PMID: <searchLink fieldCode="PM" term="%2234063813%22">34063813)</searchLink><br />Nucleic Acids Res. 2016 Aug 19;44(14):6614-24. (PMID: <searchLink fieldCode="PM" term="%2227342282%22">27342282)</searchLink><br />Antibiotics (Basel). 2023 Sep 14;12(9):. (PMID: <searchLink fieldCode="PM" term="%2237760742%22">37760742)</searchLink><br />Methods Mol Biol. 2015;1228:15-23. (PMID: <searchLink fieldCode="PM" term="%2225311118%22">25311118)</searchLink><br />BMC Microbiol. 2019 May 9;19(1):91. (PMID: <searchLink fieldCode="PM" term="%2231072343%22">31072343)</searchLink><br />Nat Rev Microbiol. 2011 Mar;9(3):215-22. (PMID: <searchLink fieldCode="PM" term="%2221297670%22">21297670)</searchLink><br />EMBO Mol Med. 2018 Oct;10(10):. (PMID: <searchLink fieldCode="PM" term="%2230171089%22">30171089)</searchLink><br />J Immunol. 2000 Apr 1;164(7):3713-22. (PMID: <searchLink fieldCode="PM" term="%2210725730%22">10725730)</searchLink><br />Science. 2000 Jun 30;288(5475):2351-4. (PMID: <searchLink fieldCode="PM" term="%2210875917%22">10875917)</searchLink><br />Front Cell Dev Biol. 2025 Feb 27;13:1534281. (PMID: <searchLink fieldCode="PM" term="%2240083666%22">40083666)</searchLink><br />Scand J Immunol. 2005 Jun;61(6):536-44. (PMID: <searchLink fieldCode="PM" term="%2215963048%22">15963048)</searchLink><br />Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):10794-9. (PMID: <searchLink fieldCode="PM" term="%2223754403%22">23754403)</searchLink><br />Med Microbiol Immunol. 2019 Oct;208(5):585-607. (PMID: <searchLink fieldCode="PM" term="%2230483863%22">30483863)</searchLink><br />Nat Commun. 2025 Dec 10;16(1):10907. (PMID: <searchLink fieldCode="PM" term="%2241372130%22">41372130)</searchLink><br />J Exp Med. 2018 Mar 05;215(3):985-997. (PMID: <searchLink fieldCode="PM" term="%2229436394%22">29436394)</searchLink><br />Bioinformatics. 2015 Nov 15;31(22):3691-3. (PMID: <searchLink fieldCode="PM" term="%2226198102%22">26198102)</searchLink><br />Front Microbiol. 2020 Jul 15;11:1643. (PMID: <searchLink fieldCode="PM" term="%2232760383%22">32760383)</searchLink><br />Cell Commun Signal. 2019 Aug 5;17(1):90. (PMID: <searchLink fieldCode="PM" term="%2231382980%22">31382980)</searchLink><br />Microbiol Res. 2017 Dec;205:19-24. (PMID: <searchLink fieldCode="PM" term="%2228942840%22">28942840)</searchLink><br />Eur J Immunol. 2020 Aug;50(8):1174-1186. (PMID: <searchLink fieldCode="PM" term="%2232250445%22">32250445)</searchLink><br />Cell Death Differ. 2004 May;11(5):550-63. (PMID: <searchLink fieldCode="PM" term="%2214739942%22">14739942)</searchLink><br />Genome Biol. 2014;15(12):550. (PMID: <searchLink fieldCode="PM" term="%2225516281%22">25516281)</searchLink><br />Eur Cell Mater. 2014 Oct 23;28:258-68. (PMID: <searchLink fieldCode="PM" term="%2225340805%22">25340805)</searchLink><br />PLoS One. 2019 Apr 1;14(4):e0214586. (PMID: <searchLink fieldCode="PM" term="%2230934018%22">30934018)</searchLink><br />EMBO J. 1999 Jun 1;18(11):3034-43. (PMID: <searchLink fieldCode="PM" term="%2210357816%22">10357816)</searchLink><br />Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6721-5. (PMID: <searchLink fieldCode="PM" term="%228692885%22">8692885)</searchLink><br />Genome Announc. 2017 Feb 23;5(8):. (PMID: <searchLink fieldCode="PM" term="%2228232428%22">28232428)</searchLink><br />Adv Exp Med Biol. 2025;1481:241-292. (PMID: <searchLink fieldCode="PM" term="%2241004085%22">41004085)</searchLink><br />PLoS Pathog. 2015 Apr 29;11(4):e1004870. (PMID: <searchLink fieldCode="PM" term="%2225923704%22">25923704)</searchLink><br />Nucleic Acids Res. 2023 Jul 5;51(W1):W207-W212. (PMID: <searchLink fieldCode="PM" term="%2237144459%22">37144459)</searchLink><br />Int J Med Microbiol. 2018 Jul;308(5):505-513. (PMID: <searchLink fieldCode="PM" term="%2229739668%22">29739668)</searchLink><br />Cell Microbiol. 2003 Oct;5(10):729-41. (PMID: <searchLink fieldCode="PM" term="%2212969378%22">12969378)</searchLink><br />Infect Immun. 2000 Sep;68(9):5385-92. (PMID: <searchLink fieldCode="PM" term="%2210948168%22">10948168)</searchLink><br />Front Immunol. 2023 Mar 31;14:1046374. (PMID: <searchLink fieldCode="PM" term="%2237063823%22">37063823)</searchLink><br />Int J Med Microbiol. 2004 Sep;294(2-3):195-202. (PMID: <searchLink fieldCode="PM" term="%2215493830%22">15493830)</searchLink><br />J Clin Invest. 2006 Nov;116(11):2901-13. (PMID: <searchLink fieldCode="PM" term="%2217024246%22">17024246)</searchLink><br />PLoS One. 2010 Nov 15;5(11):e13984. (PMID: <searchLink fieldCode="PM" term="%2221085593%22">21085593)</searchLink><br />Virulence. 2025 Dec;16(1):2553789. (PMID: <searchLink fieldCode="PM" term="%2240888369%22">40888369)</searchLink><br />PLoS Negl Trop Dis. 2017 Jan 3;11(1):e0005241. (PMID: <searchLink fieldCode="PM" term="%2228045926%22">28045926)</searchLink><br />J Transl Med. 2025 Jan 15;23(1):71. (PMID: <searchLink fieldCode="PM" term="%2239815286%22">39815286)</searchLink><br />J Cell Sci. 2002 Jul 1;115(Pt 13):2757-70. (PMID: <searchLink fieldCode="PM" term="%2212077366%22">12077366)</searchLink><br />mBio. 2018 Jul 17;9(4):. (PMID: <searchLink fieldCode="PM" term="%2230018109%22">30018109)</searchLink><br />Transl Oncol. 2021 Jan;14(1):100922. (PMID: <searchLink fieldCode="PM" term="%2233137543%22">33137543)</searchLink><br />Infect Immun. 2015 Oct 26;84(1):241-53. (PMID: <searchLink fieldCode="PM" term="%2226502911%22">26502911)</searchLink><br />Cell Microbiol. 2017 Dec;19(12):. (PMID: <searchLink fieldCode="PM" term="%2228873268%22">28873268)</searchLink><br />Front Pharmacol. 2023 Jul 24;14:1169327. (PMID: <searchLink fieldCode="PM" term="%2237554981%22">37554981)</searchLink><br />Cell Prolif. 2026 Aug;59(8):e70196. (PMID: <searchLink fieldCode="PM" term="%2241815017%22">41815017)</searchLink><br />Appl Environ Microbiol. 2020 Aug 18;86(17):. (PMID: <searchLink fieldCode="PM" term="%2232591386%22">32591386)</searchLink><br />Infect Immun. 2015 Sep;83(9):3445-57. (PMID: <searchLink fieldCode="PM" term="%2226099586%22">26099586)</searchLink><br />Microbiology (Reading). 2008 Oct;154(Pt 10):3033-3041. (PMID: <searchLink fieldCode="PM" term="%2218832309%22">18832309)</searchLink><br />Infect Immun. 1996 Aug;64(8):2974-9. (PMID: <searchLink fieldCode="PM" term="%228757823%22">8757823)</searchLink><br />mBio. 2022 Oct 26;13(5):e0231622. (PMID: <searchLink fieldCode="PM" term="%2236102512%22">36102512)</searchLink><br />Signal Transduct Target Ther. 2021 Mar 29;6(1):128. (PMID: <searchLink fieldCode="PM" term="%2233776057%22">33776057)</searchLink><br />Oncotarget. 2016 Nov 15;7(46):75774-75789. (PMID: <searchLink fieldCode="PM" term="%2227716614%22">27716614)</searchLink><br />Curr Opin Immunol. 2019 Oct;60:103-110. (PMID: <searchLink fieldCode="PM" term="%2231228759%22">31228759)</searchLink><br />Trends Cell Biol. 2015 Jun;25(6):339-46. (PMID: <searchLink fieldCode="PM" term="%2225680230%22">25680230)</searchLink><br />PLoS Pathog. 2021 Sep 2;17(9):e1009874. (PMID: <searchLink fieldCode="PM" term="%2234473800%22">34473800)</searchLink><br />J Innate Immun. 2010;2(6):560-75. (PMID: <searchLink fieldCode="PM" term="%2220587998%22">20587998)</searchLink><br />Clin Immunol. 2022 May;238:109018. (PMID: <searchLink fieldCode="PM" term="%2235460903%22">35460903)</searchLink><br />Front Cell Infect Microbiol. 2012 Apr 24;2:43. (PMID: <searchLink fieldCode="PM" term="%2222919634%22">22919634)</searchLink><br />Genome Res. 2014 May;24(5):839-49. (PMID: <searchLink fieldCode="PM" term="%2224717264%22">24717264)</searchLink><br />Nat Methods. 2020 Dec;17(12):1229-1236. (PMID: <searchLink fieldCode="PM" term="%2233257825%22">33257825)</searchLink><br />Front Cell Infect Microbiol. 2022 Apr 07;12:854242. (PMID: <searchLink fieldCode="PM" term="%2235531332%22">35531332)</searchLink><br />Front Cell Infect Microbiol. 2025 Oct 30;15:1644443. (PMID: <searchLink fieldCode="PM" term="%2241245260%22">41245260)</searchLink><br />Ann Rheum Dis. 2014 Sep;73(9):1673-6. (PMID: <searchLink fieldCode="PM" term="%2223740236%22">23740236)</searchLink><br />Immunobiology. 2020 Mar;225(2):151887. (PMID: <searchLink fieldCode="PM" term="%2231822434%22">31822434)</searchLink><br />PLoS Pathog. 2018 Jun 14;14(6):e1007112. (PMID: <searchLink fieldCode="PM" term="%2229902272%22">29902272)</searchLink><br />Cell Microbiol. 2014 Apr;16(4):451-65. (PMID: <searchLink fieldCode="PM" term="%2224164701%22">24164701)</searchLink><br />Nat Protoc. 2019 Feb;14(2):482-517. (PMID: <searchLink fieldCode="PM" term="%2230664679%22">30664679)</searchLink><br />Cell Host Microbe. 2010 Jan 21;7(1):38-49. (PMID: <searchLink fieldCode="PM" term="%2220114027%22">20114027)</searchLink><br />Cell. 2003 Jul 25;114(2):181-90. (PMID: <searchLink fieldCode="PM" term="%2212887920%22">12887920)</searchLink><br />Autoimmun Rev. 2012 Dec;12(2):225-9. (PMID: <searchLink fieldCode="PM" term="%2222796281%22">22796281)</searchLink><br />Int J Med Microbiol. 2014 Mar;304(2):170-6. (PMID: <searchLink fieldCode="PM" term="%2224365645%22">24365645)</searchLink><br />PLoS One. 2013;8(1):e53589. (PMID: <searchLink fieldCode="PM" term="%2223349721%22">23349721)</searchLink><br />Bone Joint Res. 2022 May;11(5):327-341. (PMID: <searchLink fieldCode="PM" term="%2235604422%22">35604422)</searchLink><br />Cell Microbiol. 2005 Aug;7(8):1087-97. (PMID: <searchLink fieldCode="PM" term="%2216008576%22">16008576)</searchLink><br />Clin Microbiol Infect. 2026 Jun;32(6):886-888. (PMID: <searchLink fieldCode="PM" term="%2241856403%22">41856403)</searchLink><br />Infect Immun. 1999 Aug;67(8):4201-7. (PMID: <searchLink fieldCode="PM" term="%2210417192%22">10417192)</searchLink><br />J Proteomics. 2020 Jul 15;223:103821. (PMID: <searchLink fieldCode="PM" term="%2232417293%22">32417293)</searchLink><br />Immunology. 1996 Apr;87(4):544-50. (PMID: <searchLink fieldCode="PM" term="%228675207%22">8675207)</searchLink><br />Cell Death Differ. 2003 Nov;10(11):1260-72. (PMID: <searchLink fieldCode="PM" term="%2212894214%22">12894214)</searchLink><br />Nat Protoc. 2016 Apr;11(4):795-812. (PMID: <searchLink fieldCode="PM" term="%2227010757%22">27010757)</searchLink><br />Pathog Glob Health. 2024 May;118(3):209-231. (PMID: <searchLink fieldCode="PM" term="%2238006316%22">38006316)</searchLink><br />PLoS One. 2009 Oct 14;4(10):e7446. (PMID: <searchLink fieldCode="PM" term="%2219826485%22">19826485)</searchLink><br />Cold Spring Harb Perspect Med. 2012 Dec 01;2(12):a010272. (PMID: <searchLink fieldCode="PM" term="%2223209181%22">23209181)</searchLink><br />BMC Microbiol. 2010 Nov 02;10:275. (PMID: <searchLink fieldCode="PM" term="%2221044323%22">21044323)</searchLink><br />Curr Rheumatol Rep. 2008 Oct;10(5):383-9. (PMID: <searchLink fieldCode="PM" term="%2218817643%22">18817643)</searchLink><br />Mol Immunol. 2008 Apr;45(7):2087-96. (PMID: <searchLink fieldCode="PM" term="%2218022234%22">18022234)</searchLink><br />Nature. 2009 Aug 27;460(7259):1159-63. (PMID: <searchLink fieldCode="PM" term="%2219641494%22">19641494)</searchLink><br />Trop Med Int Health. 1998 Mar;3(3):242-8. (PMID: <searchLink fieldCode="PM" term="%229593364%22">9593364)</searchLink><br />J Infect Dis. 2024 Dec 16;230(6):1488-1500. (PMID: <searchLink fieldCode="PM" term="%2238805184%22">38805184)</searchLink><br />Cell Microbiol. 2016 Nov;18(11):1583-1595. (PMID: <searchLink fieldCode="PM" term="%2227062399%22">27062399)</searchLink><br />Traffic. 2019 Mar;20(3):246-258. (PMID: <searchLink fieldCode="PM" term="%2230569578%22">30569578)</searchLink><br />Immunol Res. 2019 Jun;67(2-3):241-260. (PMID: <searchLink fieldCode="PM" term="%2231290001%22">31290001)</searchLink><br />PLoS Pathog. 2016 Sep 15;12(9):e1005857. (PMID: <searchLink fieldCode="PM" term="%2227632173%22">27632173)</searchLink><br />Mol Cell Proteomics. 2019 May;18(5):892-908. (PMID: <searchLink fieldCode="PM" term="%2230808728%22">30808728)</searchLink><br />Front Pharmacol. 2021 Nov 01;12:746396. (PMID: <searchLink fieldCode="PM" term="%2234790122%22">34790122)</searchLink><br />Bioinformatics. 2013 Jan 1;29(1):15-21. (PMID: <searchLink fieldCode="PM" term="%2223104886%22">23104886)</searchLink><br />Nat Commun. 2023 Jul 18;14(1):4290. (PMID: <searchLink fieldCode="PM" term="%2237463962%22">37463962)</searchLink><br />BMC Bioinformatics. 2020 Apr 10;21(1):139. (PMID: <searchLink fieldCode="PM" term="%2232272889%22">32272889)</searchLink><br />Traffic. 2013 Mar;14(3):321-36. (PMID: <searchLink fieldCode="PM" term="%2223231467%22">23231467)</searchLink><br />Infect Immun. 2003 May;71(5):2716-23. (PMID: <searchLink fieldCode="PM" term="%2212704146%22">12704146)</searchLink><br />Nat Methods. 2020 Jan;17(1):41-44. (PMID: <searchLink fieldCode="PM" term="%2231768060%22">31768060)</searchLink><br />Appl Environ Microbiol. 2025 Aug 20;91(8):e0021125. (PMID: <searchLink fieldCode="PM" term="%2240679283%22">40679283)</searchLink><br />Nat Commun. 2022 Nov 22;13(1):7174. (PMID: <searchLink fieldCode="PM" term="%2236418309%22">36418309)</searchLink><br />J Bacteriol. 1991 Oct;173(20):6313-20. (PMID: <searchLink fieldCode="PM" term="%221717437%22">1717437)</searchLink><br />Sci Adv. 2023 Jun 16;9(24):eadf8748. (PMID: <searchLink fieldCode="PM" term="%2237327341%22">37327341)</searchLink><br />J Neuroinflammation. 2024 Jul 23;21(1):179. (PMID: <searchLink fieldCode="PM" term="%2239044282%22">39044282)</searchLink><br />Front Immunol. 2020 Nov 11;11:565545. (PMID: <searchLink fieldCode="PM" term="%2233262756%22">33262756)</searchLink><br />PLoS One. 2017 Aug 9;12(8):e0182415. (PMID: <searchLink fieldCode="PM" term="%2228793310%22">28793310)</searchLink><br />Infect Immun. 2014 Oct;82(10):4144-53. (PMID: <searchLink fieldCode="PM" term="%2225047846%22">25047846)</searchLink><br />Nat Methods. 2009 May;6(5):359-62. (PMID: <searchLink fieldCode="PM" term="%2219377485%22">19377485)</searchLink><br />Proc Natl Acad Sci U S A. 2022 Aug 2;119(31):e2123017119. (PMID: <searchLink fieldCode="PM" term="%2235881802%22">35881802)</searchLink><br />PLoS Pathog. 2015 Jun 12;11(6):e1004970. (PMID: <searchLink fieldCode="PM" term="%2226069969%22">26069969)</searchLink><br />Nucleic Acids Res. 2017 Jan 4;45(D1):D1107-D1111. (PMID: <searchLink fieldCode="PM" term="%2227899654%22">27899654)</searchLink><br />Sci Rep. 2021 Mar 16;11(1):6037. (PMID: <searchLink fieldCode="PM" term="%2233727596%22">33727596)</searchLink><br />Am J Physiol Cell Physiol. 2025 Nov 1;329(5):C1672-C1680. (PMID: <searchLink fieldCode="PM" term="%2241117409%22">41117409)</searchLink><br />Front Cell Infect Microbiol. 2019 Mar 07;9:57. (PMID: <searchLink fieldCode="PM" term="%2230899700%22">30899700)</searchLink><br />Science. 1999 Jan 22;283(5401):543-6. (PMID: <searchLink fieldCode="PM" term="%229915703%22">9915703)</searchLink><br />Physiol Rev. 2019 Jan 1;99(1):115-160. (PMID: <searchLink fieldCode="PM" term="%2230354964%22">30354964)</searchLink><br />Inflamm Bowel Dis. 2023 Mar 1;29(3):339-348. (PMID: <searchLink fieldCode="PM" term="%2235776552%22">35776552)</searchLink><br />Cell Microbiol. 2016 Apr;18(4):514-35. (PMID: <searchLink fieldCode="PM" term="%2226408990%22">26408990)</searchLink><br />Clin Microbiol Infect. 2026 Jun;32(6):951-958. (PMID: <searchLink fieldCode="PM" term="%2241690515%22">41690515)</searchLink><br />Sci Rep. 2023 Jan 21;13(1):1188. (PMID: <searchLink fieldCode="PM" term="%2236681703%22">36681703)</searchLink><br />Int J Med Microbiol. 2018 Aug;308(6):607-624. (PMID: <searchLink fieldCode="PM" term="%2229217333%22">29217333)</searchLink><br />Clin Microbiol Infect. 2016 Sep;22(9):799-809. (PMID: <searchLink fieldCode="PM" term="%2227393124%22">27393124)</searchLink><br />Infect Immun. 1970 Oct;2(4):387-91. (PMID: <searchLink fieldCode="PM" term="%2216557850%22">16557850)</searchLink><br />Nat Methods. 2012 Jul;9(7):671-5. (PMID: <searchLink fieldCode="PM" term="%2222930834%22">22930834)</searchLink><br />Clin Infect Dis. 2001 Jun 1;32(11):1643-7. (PMID: <searchLink fieldCode="PM" term="%2211340539%22">11340539)</searchLink><br />PLoS One. 2015 Feb 26;10(2):e0117713. (PMID: <searchLink fieldCode="PM" term="%2225719526%22">25719526)</searchLink><br />J Bacteriol. 2002 Oct;184(19):5457-67. (PMID: <searchLink fieldCode="PM" term="%2212218034%22">12218034)</searchLink><br />Cell Microbiol. 2019 Mar;21(3):e12997. (PMID: <searchLink fieldCode="PM" term="%2230576050%22">30576050)</searchLink><br />PLoS Pathog. 2021 Jan 21;17(1):e1009184. (PMID: <searchLink fieldCode="PM" term="%2233476322%22">33476322)</searchLink><br />Cell Res. 2015 Jun;25(6):707-25. (PMID: <searchLink fieldCode="PM" term="%2225952668%22">25952668)</searchLink><br />J Infect Dis. 2012 Oct;206(8):1185-93. (PMID: <searchLink fieldCode="PM" term="%2222872735%22">22872735)</searchLink><br />Virchows Arch B Cell Pathol. 1973;14(1):35-45. (PMID: <searchLink fieldCode="PM" term="%224355691%22">4355691)</searchLink><br />Thorac Cancer. 2019 Mar;10(3):437-444. (PMID: <searchLink fieldCode="PM" term="%2230628200%22">30628200)</searchLink><br />Bioinformatics. 2014 Jul 15;30(14):2068-9. (PMID: <searchLink fieldCode="PM" term="%2224642063%22">24642063)</searchLink><br />J Infect Dis. 1992 Jul;166(1):58-64. (PMID: <searchLink fieldCode="PM" term="%221607709%22">1607709)</searchLink><br />Front Cell Infect Microbiol. 2026 Jun 15;16:1840752. (PMID: <searchLink fieldCode="PM" term="%2242376318%22">42376318)</searchLink><br />J Biol Chem. 2007 Jan 26;282(4):2695-706. (PMID: <searchLink fieldCode="PM" term="%2217135247%22">17135247)</searchLink><br />PLoS Pathog. 2015 Apr 16;11(4):e1004820. (PMID: <searchLink fieldCode="PM" term="%2225880560%22">25880560)</searchLink><br />J Clin Invest. 2024 Oct 1;134(19):. (PMID: <searchLink fieldCode="PM" term="%2239352382%22">39352382)</searchLink><br />Bone Marrow Transplant. 1992 May;9(5):369-76. (PMID: <searchLink fieldCode="PM" term="%221617321%22">1617321)</searchLink><br />Infect Immun. 1998 Jan;66(1):336-42. (PMID: <searchLink fieldCode="PM" term="%229423876%22">9423876)</searchLink><br />J Transl Med. 2019 Jul 2;17(1):215. (PMID: <searchLink fieldCode="PM" term="%2231266509%22">31266509)</searchLink>
– Name: GrantInfo
  Label: Grant Information
  Group: Grant
  Data: 318346496, 446605368 Deutsche Forschungsgemeinschaft; 422048538, 467522186 Deutsche Forschungsgemeinschaft; 547933897 Deutsche Forschungsgemeinschaft
– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: <i>Keywords: </i>Staphylococcus aureus; Apoptosis; Host cell death; Host response; Host‒pathogen interactions; Intracellular infection; Perinuclear; TNF receptor 1; TNF-α; Transcriptomics<br /><i>Local Abstract: </i>[plain-language-summary] The bacterium Staphylococcus aureus (S. aureus) often lives harmlessly in humans but can cause severe or recurrent infections when the skin barrier is broken or when the immune system is weakened. A major reason for its persistence is its ability to hide inside human cells, where it is shielded from immune attacks and antibiotics. To effectively target such bacteria, it is crucial to understand that infections vary depending on both the bacterial strain and the infected tissue type. Many reasons behind these differences are still puzzling. We explored how different types of S. aureus (collected from different disease types) change how different human cells respond to infection. We focused on how each strain influences the way immune cells adjust their gene activity during infection, and how a receptor called TNF‑R1 is involved in managing cell death responses.Bacteria are found in compartments meant to destroy them but frequently also in close association to the cell nucleus, an unexpected location that requires further investigation. All strains triggered a similar stress response but also distinct patterns differentially influencing inflammation, metabolism, and cell survival. A strain linked to chronic infection caused weaker responses, suggesting greater ability to remain undetected. The immune cells had greater presence of TNF-R1 on their surface when infected, and when they lacked this receptor entirely, they initially survived longer but later showed greater damage, indicating its key role in infection control. In lung and bone cells, these effects were less pronounced.In conclusion, S. aureus uses various survival strategies that have heterogeneous impact on different host tissues. Some bacteria localized to unexpected compartments close to the cell’s control center inside all analyzed human cell types. Importantly, while the exact mechanisms are not yet clear, TNF-R1 influences host infection responses in the studied immune cells, highlighting that the interaction of bacterial programs and critical host factors must be carefully considered when developing targeted treatments.
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: 0 (Receptors, Tumor Necrosis Factor, Type I)
– Name: DateEntry
  Label: Entry Date(s)
  Group: Date
  Data: <i>Date Created: </i>20260929 <i>Date Completed: </i>20260930 <i>Latest Revision: </i>20261001
– Name: DateUpdate
  Label: Update Code
  Group: Date
  Data: 20261001
– Name: PubmedCentralID
  Label: PubMed Central ID
  Group: ID
  Data: PMC13621601
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1186/s12964-026-03246-8
– Name: AN
  Label: PMID
  Group: ID
  Data: 42811321
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42811321
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1186/s12964-026-03246-8
    Languages:
      – Code: eng
        Text: English
    Subjects:
      – SubjectFull: Monocytes microbiology
        Type: general
      – SubjectFull: Monocytes metabolism
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: U937 Cells
        Type: general
      – SubjectFull: Signal Transduction
        Type: general
      – SubjectFull: Apoptosis
        Type: general
      – SubjectFull: Staphylococcus aureus isolation & purification
        Type: general
      – SubjectFull: Staphylococcus aureus physiology
        Type: general
      – SubjectFull: Receptors, Tumor Necrosis Factor, Type I metabolism
        Type: general
      – SubjectFull: Receptors, Tumor Necrosis Factor, Type I genetics
        Type: general
      – SubjectFull: Host-Pathogen Interactions genetics
        Type: general
      – SubjectFull: Intracellular Space microbiology
        Type: general
      – SubjectFull: Transcription, Genetic
        Type: general
    Titles:
      – TitleFull: Intracellular Staphylococcus aureus triggers isolate-specific host transcriptional responses alongside TNF-R1 regulated cell fate decisions.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Walter A
      – PersonEntity:
          Name:
            NameFull: Bischler T
      – PersonEntity:
          Name:
            NameFull: Jungblut M
      – PersonEntity:
          Name:
            NameFull: Breitsprecher LF
      – PersonEntity:
          Name:
            NameFull: Vilotic F
      – PersonEntity:
          Name:
            NameFull: Beck J
      – PersonEntity:
          Name:
            NameFull: Hofmann L
      – PersonEntity:
          Name:
            NameFull: Schäfer N
      – PersonEntity:
          Name:
            NameFull: Ziesmann T
      – PersonEntity:
          Name:
            NameFull: Franzkoch R
      – PersonEntity:
          Name:
            NameFull: Härteis S
      – PersonEntity:
          Name:
            NameFull: Gadjalova I
      – PersonEntity:
          Name:
            NameFull: Distler U
      – PersonEntity:
          Name:
            NameFull: Beliu G
      – PersonEntity:
          Name:
            NameFull: Psathaki OE
      – PersonEntity:
          Name:
            NameFull: Hensel M
      – PersonEntity:
          Name:
            NameFull: Schneider-Brachert W
      – PersonEntity:
          Name:
            NameFull: Gräfenhan T
      – PersonEntity:
          Name:
            NameFull: Stempfl T
      – PersonEntity:
          Name:
            NameFull: Kieninger B
      – PersonEntity:
          Name:
            NameFull: Mühlen S
      – PersonEntity:
          Name:
            NameFull: Alt V
      – PersonEntity:
          Name:
            NameFull: Mannala GK
      – PersonEntity:
          Name:
            NameFull: Fritsch J
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 28
              M: 09
              Text: 2026 Sep 28
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1478-811X
          Numbering:
            – Type: volume
              Value: 24
            – Type: issue
              Value: 1
          Titles:
            – TitleFull: Cell communication and signaling : CCS
              Type: main
ResultId 1