Academic Journal
Προβολή σε EDS

Complement receptor 2 downregulation is associated with mortality in Staphylococcus aureus sepsis in both mice and humans.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Complement receptor 2 downregulation is associated with mortality in Staphylococcus aureus sepsis in both mice and humans.
Συγγραφείς: Kopparapu PK; Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Deshmukh M; Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Subhash S; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, United States.; Department of Biosciences and Bioengineering, Indian Institute of Technology Jammu, Jammu, Jammu and Kashmir, India., Mohammad M; Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Hu Z; Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, China., Jarneborn A; Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Department of Rheumatology, Sahlgrenska University Hospital, Gothenburg, Sweden., Arif M; Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Science for Life Laboratory, University of Gothenburg, Gothenburg, Sweden., Pekna M; Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Ljungström L; Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden., Jacobsson G; Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden., Grimsholm O; Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Jin T; Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Department of Rheumatology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Πηγή: Frontiers in immunology [Front Immunol] 2026 Jul 09; Vol. 17, pp. 1724049. Date of Electronic Publication: 2026 Jul 09 (Print Publication: 2026).
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
Imprint Name(s): Original Publication: [Lausanne : Frontiers Research Foundation]
Ιατρικοί όροι (MeSH): Staphylococcal Infections*/mortality , Staphylococcal Infections*/immunology , Staphylococcal Infections*/genetics , Staphylococcal Infections*/microbiology , Sepsis*/mortality , Sepsis*/immunology , Sepsis*/microbiology , Sepsis*/genetics , Staphylococcus aureus*/immunology , Receptors, Complement 3d*/genetics , Receptors, Complement 3d*/metabolism, B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Animals ; Humans ; Mice ; Down-Regulation ; Disease Models, Animal ; Male ; Biomarkers ; Female ; Mice, Inbred C57BL
Περίληψη: Although sepsis is a leading cause of global mortality, the lack of reliable biomarkers hinders early risk stratification. Such biomarkers would facilitate timely and precise therapeutic interventions. Using a murine model of Staphylococcus aureus (S. aureus) sepsis, we performed transcriptomic analysis and identified numerous genes that distinguished survivors from fatal cases. The top 16 candidate genes were further evaluated in patients with severe invasive bacterial infections. Among these, complement receptor 2 (CR2) was significantly downregulated in deceased patients compared with survivors and healthy controls. The extent of CR2 downregulation was dependent on the administered dose of S. aureus. Time-course experiments conducted in infected mice showed progressive B-cell depletion and CR2 downregulation, correlating with disease severity. Importantly, CR2 downregulation was independent of complement factor 3, TLR2, and tumor necrosis (TNF)-α, but was reversed in infections with S. aureus strains that lacked sortase A and B, and restored by antibiotic treatment of the infected mice. Loss of CR2 expression may reflect B-cell activation followed by differentiation into plasmablasts and redistribution to secondary lymphoid organs. The present study suggests that CR2 downregulation is associated with severe infection and mortality in S. aureus sepsis and may represent a candidate biomarker of host immune dysregulation that warrants further validation in larger clinical cohorts.
(Copyright © 2026 Kopparapu, Deshmukh, Subhash, Mohammad, Hu, Jarneborn, Arif, Pekna, Ljungström, Jacobsson, Grimsholm and Jin.)
Competing Interests: The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author TJ declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
References: Crit Care Med. 2017 May;45(5):875-882. (PMID: 28296810)
Crit Care. 2010;14(3):R96. (PMID: 20504311)
J Immunol. 2001 Jun 1;166(11):6952-63. (PMID: 11359857)
J Clin Invest. 2002 Jul;110(1):101-8. (PMID: 12093893)
J Crit Care. 2013 Dec;28(6):1032-8. (PMID: 24216332)
Clin Microbiol Rev. 2012 Apr;25(2):362-86. (PMID: 22491776)
Crit Care Med. 2018 Jun;46(6):e489-e495. (PMID: 29432347)
Am J Emerg Med. 2020 Mar;38(3):641-647. (PMID: 31785981)
Shock. 2023 Sep 1;60(3):345-353. (PMID: 37477437)
J Infect Dis. 2011 Aug 1;204(3):348-57. (PMID: 21742832)
BMC Res Notes. 2014 Jul 17;7:458. (PMID: 25034373)
Shock. 2014 Nov;42(5):383-91. (PMID: 25051284)
J Immunol. 2000 Dec 15;165(12):6915-21. (PMID: 11120817)
Immunity. 2021 Nov 9;54(11):2450-2464. (PMID: 34758337)
Bioinformatics. 2014 Apr 1;30(7):923-30. (PMID: 24227677)
Intensive Care Med. 2016 Dec;42(12):2027-2029. (PMID: 27815587)
Proc Natl Acad Sci U S A. 2003 May 27;100(11):6724-9. (PMID: 12736377)
PLoS Pathog. 2019 Jun 21;15(6):e1007877. (PMID: 31226163)
Crit Care Med. 2001 Jul;29(7):1303-10. (PMID: 11445675)
Lancet. 2023 Dec 17;400(10369):2221-2248. (PMID: 36423648)
Sci Rep. 2020 May 13;10(1):7936. (PMID: 32404866)
Nucleic Acids Res. 2021 Jan 8;49(D1):D916-D923. (PMID: 33270111)
Int J Mol Sci. 2021 Jul 01;22(13):. (PMID: 34281154)
JAMA Netw Open. 2019 Aug 2;2(8):e198686. (PMID: 31390038)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2293-8. (PMID: 11830639)
J Exp Med. 2011 Aug 1;208(8):1673-82. (PMID: 21746813)
Nat Rev Microbiol. 2014 Jan;12(1):49-62. (PMID: 24336184)
Am J Pathol. 2007 Sep;171(3):715-27. (PMID: 17640961)
Science. 1996 Jan 19;271(5247):348-50. (PMID: 8553069)
JAMA. 2014 Oct 1;312(13):1330-41. (PMID: 25268440)
BMC Res Notes. 2021 Feb 27;14(1):76. (PMID: 33640018)
Front Microbiol. 2023 Jun 15;14:1146694. (PMID: 37396347)
J Infect Dis. 2015 Oct 15;212(8):1308-16. (PMID: 25838268)
Gigascience. 2021 Feb 16;10(2):. (PMID: 33590861)
Shock. 2020 Jul;54(1):70-77. (PMID: 31764616)
J Inflamm Res. 2021 Aug 11;14:3837-3848. (PMID: 34408466)
Crit Care Med. 2020 Jun;48(6):815-821. (PMID: 32304414)
Front Microbiol. 2022 Oct 03;13:1006765. (PMID: 36262324)
J Leukoc Biol. 2005 Aug;78(2):325-37. (PMID: 15817707)
Shock. 2024 Feb 1;61(2):197-203. (PMID: 38151771)
Nat Methods. 2015 Apr;12(4):357-60. (PMID: 25751142)
Lancet Respir Med. 2024 Apr;12(4):305-322. (PMID: 38142698)
Microbes Infect. 2003 Jul;5(9):775-80. (PMID: 12850203)
Expert Rev Anti Infect Ther. 2012 Jun;10(6):701-6. (PMID: 22734959)
Surg Infect (Larchmt). 2013 Dec;14(6):489-511. (PMID: 24274059)
Nucleic Acids Res. 2022 Jan 7;50(D1):D988-D995. (PMID: 34791404)
Nat Immunol. 2004 Oct;5(10):981-6. (PMID: 15454921)
J Gen Microbiol. 1952 Feb;6(1-2):95-107. (PMID: 14927856)
BMC Bioinformatics. 2016 Sep 13;17(1):365. (PMID: 27618934)
Annu Rev Immunol. 1995;13:127-49. (PMID: 7542009)
Front Immunol. 2024 Sep 18;15:1437864. (PMID: 39359725)
Contributed Indexing: Keywords: B cells; biomarkers; complement receptor 2; mortality; rna sequencing; sepsis
Substance Nomenclature: 0 (Biomarkers)
0 (Receptors, Complement 3d)
Entry Date(s): Date Created: 20260724 Date Completed: 20260724 Latest Revision: 20260813
Update Code: 20260814
PubMed Central ID: PMC13391265
DOI: 10.3389/fimmu.2026.1724049
PMID: 42495651
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1664-3224
DOI:10.3389/fimmu.2026.1724049