Cryptococcus neoformans Δsgl1 Vaccination Requires Either CD4+ or CD8+ T Cells for Complete Host Protection
Cryptococcus neoformans is a fungal pathogen causing life-threatening meningoencephalitis in susceptible individuals. Fungal vaccine development has been hampered by the fact that cryptococcosis occurs during immunodeficiency. We previously reported that a C. neoformans mutant (Δsgl1) accumulating s...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2021.739027/full |
| _version_ | 1818734862209646592 |
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| author | Tyler G. Normile Antonella Rella Maurizio Del Poeta Maurizio Del Poeta Maurizio Del Poeta |
| author_facet | Tyler G. Normile Antonella Rella Maurizio Del Poeta Maurizio Del Poeta Maurizio Del Poeta |
| author_sort | Tyler G. Normile |
| collection | DOAJ |
| description | Cryptococcus neoformans is a fungal pathogen causing life-threatening meningoencephalitis in susceptible individuals. Fungal vaccine development has been hampered by the fact that cryptococcosis occurs during immunodeficiency. We previously reported that a C. neoformans mutant (Δsgl1) accumulating sterylglucosides (SGs) is avirulent and provides complete protection to WT challenge, even under CD4+ T cell depletion, an immunodeficient condition commonly associated with cryptococcosis. We found high levels of SGs in the lungs post-immunization with Δsgl1 that decreased upon fungal clearance. Th1 cytokines increased whereas Th2 cytokines concurrently decreased, coinciding with a large recruitment of leukocytes to the lungs. Depletion of B or CD8+ T cells did not affect either Δsgl1 clearance or protection from WT challenge. Although CD4+ T cell depletion affected clearance, mice were still protected indicating that clearance of the mutant was not necessary for host protection. Protection was lost only when both CD4+ and CD8+ T cells were depleted, highlighting a previously unexplored role of fungal-derived SGs as an immunoadjuvant for host protection against cryptococcosis. |
| first_indexed | 2024-12-18T00:12:06Z |
| format | Article |
| id | doaj.art-9ddd2cafa4884b4292588f6d0c5ecd06 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-18T00:12:06Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-9ddd2cafa4884b4292588f6d0c5ecd062022-12-21T21:27:39ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-09-011110.3389/fcimb.2021.739027739027Cryptococcus neoformans Δsgl1 Vaccination Requires Either CD4+ or CD8+ T Cells for Complete Host ProtectionTyler G. Normile0Antonella Rella1Maurizio Del Poeta2Maurizio Del Poeta3Maurizio Del Poeta4Department of Microbiology and Immunology, Stony Brook University, Stony Brook, NY, United StatesDepartment of Microbiology and Immunology, Stony Brook University, Stony Brook, NY, United StatesDepartment of Microbiology and Immunology, Stony Brook University, Stony Brook, NY, United StatesDivision of Infectious Diseases, School of Medicine, Stony Brook University, Stony Brook, NY, United StatesVeterans Administration Medical Center, Northport, NY, United StatesCryptococcus neoformans is a fungal pathogen causing life-threatening meningoencephalitis in susceptible individuals. Fungal vaccine development has been hampered by the fact that cryptococcosis occurs during immunodeficiency. We previously reported that a C. neoformans mutant (Δsgl1) accumulating sterylglucosides (SGs) is avirulent and provides complete protection to WT challenge, even under CD4+ T cell depletion, an immunodeficient condition commonly associated with cryptococcosis. We found high levels of SGs in the lungs post-immunization with Δsgl1 that decreased upon fungal clearance. Th1 cytokines increased whereas Th2 cytokines concurrently decreased, coinciding with a large recruitment of leukocytes to the lungs. Depletion of B or CD8+ T cells did not affect either Δsgl1 clearance or protection from WT challenge. Although CD4+ T cell depletion affected clearance, mice were still protected indicating that clearance of the mutant was not necessary for host protection. Protection was lost only when both CD4+ and CD8+ T cells were depleted, highlighting a previously unexplored role of fungal-derived SGs as an immunoadjuvant for host protection against cryptococcosis.https://www.frontiersin.org/articles/10.3389/fcimb.2021.739027/fullCryptococcus neoformanscryptococcosishost immune responseimmunodeficiencyvaccinationsterylglucosides |
| spellingShingle | Tyler G. Normile Antonella Rella Maurizio Del Poeta Maurizio Del Poeta Maurizio Del Poeta Cryptococcus neoformans Δsgl1 Vaccination Requires Either CD4+ or CD8+ T Cells for Complete Host Protection Frontiers in Cellular and Infection Microbiology Cryptococcus neoformans cryptococcosis host immune response immunodeficiency vaccination sterylglucosides |
| title | Cryptococcus neoformans Δsgl1 Vaccination Requires Either CD4+ or CD8+ T Cells for Complete Host Protection |
| title_full | Cryptococcus neoformans Δsgl1 Vaccination Requires Either CD4+ or CD8+ T Cells for Complete Host Protection |
| title_fullStr | Cryptococcus neoformans Δsgl1 Vaccination Requires Either CD4+ or CD8+ T Cells for Complete Host Protection |
| title_full_unstemmed | Cryptococcus neoformans Δsgl1 Vaccination Requires Either CD4+ or CD8+ T Cells for Complete Host Protection |
| title_short | Cryptococcus neoformans Δsgl1 Vaccination Requires Either CD4+ or CD8+ T Cells for Complete Host Protection |
| title_sort | cryptococcus neoformans δsgl1 vaccination requires either cd4 or cd8 t cells for complete host protection |
| topic | Cryptococcus neoformans cryptococcosis host immune response immunodeficiency vaccination sterylglucosides |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2021.739027/full |
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