Academic Journal
Cryptococcus displays spore-specific uptake by alveolar epithelial cells.
| Τίτλος: | Cryptococcus displays spore-specific uptake by alveolar epithelial cells. |
|---|---|
| Συγγραφείς: | Ortiz SC; Manchester Fungal Infection Group, Faculty of Biology, Medicine and Health, The University of Manchester, Core Technology Facility, Manchester, United Kingdom., Fortune-Grant R; Manchester Fungal Infection Group, Faculty of Biology, Medicine and Health, The University of Manchester, Core Technology Facility, Manchester, United Kingdom., Thom AJ; Manchester Fungal Infection Group, Faculty of Biology, Medicine and Health, The University of Manchester, Core Technology Facility, Manchester, United Kingdom., Davies J; Manchester Fungal Infection Group, Faculty of Biology, Medicine and Health, The University of Manchester, Core Technology Facility, Manchester, United Kingdom., May RC; Institute of Microbiology & Infection and School of Biosciences, University of Birmingham, Birmingham, United Kingdom., Drummond RA; Institute of Immunology & Immunotherapy, Institute of Microbiology & Infection, University of Birmingham, Birmingham, United Kingdom., Bertuzzi M; Manchester Fungal Infection Group, Faculty of Biology, Medicine and Health, The University of Manchester, Core Technology Facility, Manchester, United Kingdom. |
| Πηγή: | MBio [mBio] 2025 Nov 12; Vol. 16 (11), pp. e0183125. Date of Electronic Publication: 2025 Oct 22. |
| Τύπος έκδοσης: | Journal Article; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, D.C. : American Society for Microbiology |
| Ιατρικοί όροι (MeSH): | Cryptococcus neoformans*/physiology , Cryptococcus neoformans*/pathogenicity , Spores, Fungal*/physiology , Alveolar Epithelial Cells*/microbiology , Cryptococcosis*/microbiology, Epithelial Cells/microbiology ; Animals ; Humans ; Mice ; Host-Pathogen Interactions ; Mice, Inbred C57BL |
| Περίληψη: | Human fungal pathogens, including Cryptococcus neoformans, cause 1.5 million annual deaths. Cryptococcus causes disease when it disseminates out of the lung and into the brain, which can occur years after initial exposure (latency) via mechanisms that remain unknown. Spores of Cryptococcus display distinct surface epitopes, host interactions, and disease kinetics to the vegetatively growing yeast morphotype, yet they remain understudied, likely contributing to our lack of understanding of pathogenesis. One of the first barriers spores encounter is non-professional phagocytic airway epithelial cells (AECs). Here, we demonstrate that Cryptococcus spores are preferentially internalized by AECs both in vitro and in vivo. Once inside, spores can germinate, subsequently replicate, persist, and/or escape. This ability to enter AECs correlates with a preferential ability of spores to cross AEC barriers. Together, our work indicates that AECs internalize Cryptococcus spores and may serve as a previously ignored intracellular host niche, providing alternative hypotheses for both Cryptococcus dissemination and latency.IMPORTANCEFungal spores are a dormant, stress-resistant, and relatively understudied cell type and are presumed infectious cell types in cryptococcal disease. Cryptococcus spores have been shown to display distinct disease kinetics to the vegetative yeast morphotype and are significantly better at disseminating out of the host lung. While the molecular mechanisms by which spores disseminate out of the lung have yet to be identified, their preferential ability to get inside host cells likely enables their dissemination. Here, we show that spores, unlike yeast, readily get taken up by non-professional phagocytic cells, airway epithelial cells, both in vitro and in vivo, and once inside can germinate, replicate, escape, and/or persist. These results provide a previously unexplored host cell type that Cryptococcus can inhabit, likely affecting disease kinetics and could be a critical interaction in understanding both extrapulmonary dissemination and latency. |
| Competing Interests: | The authors declare no conflict of interest. |
| References: | J Fungi (Basel). 2018 Jan 08;4(1):. (PMID: 29371501) J Fungi (Basel). 2017 Oct 02;3(4):. (PMID: 29371569) Lancet. 2000 Dec 23-30;356(9248):2133-8. (PMID: 11191539) Infect Immun. 2009 Aug;77(8):3491-500. (PMID: 19451235) Integr Biol (Camb). 2016 May 16;8(5):603-15. (PMID: 27026574) J Infect Dis. 2019 Feb 15;219(5):685-694. (PMID: 30376080) mBio. 2021 Aug 31;12(4):e0167221. (PMID: 34311572) Eur J Clin Microbiol Infect Dis. 2015 Dec;34(12):2421-7. (PMID: 26463450) Curr Biol. 2006 Nov 7;16(21):2156-60. (PMID: 17084701) Sci Transl Med. 2012 Dec 19;4(165):165rv13. (PMID: 23253612) Curr Biol. 2006 Nov 7;16(21):2161-5. (PMID: 17084702) Infect Immun. 2010 Sep;78(9):3832-47. (PMID: 20584970) Am Rev Respir Dis. 1982 Jun;125(6):740-5. (PMID: 7091881) FEMS Microbiol Rev. 2019 Mar 1;43(2):145-161. (PMID: 30657899) Fungal Genet Biol. 2017 Nov;108:13-25. (PMID: 28870457) Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3165-70. (PMID: 11880650) Methods Mol Biol. 2021;2260:83-109. (PMID: 33405032) PLoS One. 2017 Mar 10;12(3):e0173866. (PMID: 28282442) PLoS Pathog. 2021 Mar 18;17(3):e1009342. (PMID: 33735307) FEMS Immunol Med Microbiol. 1997 Nov;19(3):203-13. (PMID: 9453390) J Clin Invest. 2020 Jul 1;130(7):3353-3360. (PMID: 32484459) Microbes Infect. 2006 Feb;8(2):493-502. (PMID: 16293436) Eukaryot Cell. 2009 Apr;8(4):595-605. (PMID: 19181873) mBio. 2024 Apr 10;15(4):e0307823. (PMID: 38511961) Lancet Infect Dis. 2017 Aug;17(8):873-881. (PMID: 28483415) Infect Immun. 2016 Sep 19;84(10):3047-62. (PMID: 27481252) J Clin Microbiol. 1999 Oct;37(10):3204-9. (PMID: 10488178) PLoS Pathog. 2019 Jun 27;15(6):e1007777. (PMID: 31247052) PLoS Pathog. 2010 Jun 17;6(6):e1000953. (PMID: 20585559) Infect Immun. 2002 Jan;70(1):140-6. (PMID: 11748175) Microbiol Mol Biol Rev. 2024 Mar 27;88(1):e0019623. (PMID: 38440970) Infect Immun. 2008 Jul;76(7):2923-38. (PMID: 18426889) J Fungi (Basel). 2017 Oct 18;3(4):. (PMID: 29371573) |
| Grant Information: | British Mycological Society; MR/V031287/1 United Kingdom MRC_ Medical Research Council; MR/S024611 United Kingdom MRC_ Medical Research Council |
| Contributed Indexing: | Keywords: C. deneoformans; Cryptococcus neoformans; airway epithelial cells; dissemination; fungal pathogenesis; latency; phagocytosis; spores |
| Entry Date(s): | Date Created: 20251022 Date Completed: 20251113 Latest Revision: 20260712 |
| Update Code: | 20260712 |
| PubMed Central ID: | PMC12607909 |
| DOI: | 10.1128/mbio.01831-25 |
| PMID: | 41123343 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2150-7511 |
|---|---|
| DOI: | 10.1128/mbio.01831-25 |