title: Tc17 cells mediate vaccine immunity against lethal fungal pneumonia in immune deficient hosts lacking CD4+ T cells.
abstract: Vaccines may help reduce the growing incidence of fungal infections in immune-suppressed patients. We have found that, even in the absence of CD4(+) T-cell help, vaccine-induced CD8(+) T cells persist and confer resistance against Blastomyces dermatitidis and Histoplasma capsulatum. Type 1 cytokines contribute to that resistance, but they also are dispensable. Although the role of T helper 17 cells in immunity to fungi is debated, IL-17 producing CD8(+) T cells (Tc17 cells) have not been investigated. Here, we show that Tc17 cells are indispensable in antifungal vaccine immunity in hosts lacking CD4(+) T cells. Tc17 cells are induced upon vaccination, recruited to the lung on pulmonary infection, and act non-redundantly in mediating protection in a manner that requires neutrophils. Tc17 cells did not influence type I immunity, nor did the lack of IL-12 signaling augment Tc17 cells, indicating a distinct lineage and function. IL-6 was required for Tc17 differentiation and immunity, but IL-1R1 and Dectin-1 signaling was unexpectedly dispensable. Tc17 cells expressed surface CXCR3 and CCR6, but only the latter was essential in recruitment to the lung. Although IL-17 producing T cells are believed to be short-lived, effector Tc17 cells expressed low levels of KLRG1 and high levels of the transcription factor TCF-1, predicting their long-term survival and stem-cell like behavior. Our work has implications for designing vaccines against fungal infections in immune suppressed patients.
authors: The Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin Madison, Madison, Wisconsin, United States of America.
authors: Som Gowda
authors: SG
authors: Nanjappa
authors: Erika
authors: E
authors: Heninger
authors: Marcel
authors: M
authors: Wüthrich
authors: David Joseph
authors: DJ
authors: Gasper
authors: Bruce S
authors: BS
authors: Klein
mesh_terms: D000818:Animals; D001758:Blastomyces / Q000276:immunology / Q000472:pathogenicity; D001759:Blastomycosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D005657:Fungal Vaccines / Q000276:immunology*; D051538:Hepatocyte Nuclear Factor 1-alpha; D006658:Histoplasma / Q000276:immunology / Q000472:pathogenicity; D006660:Histoplasmosis / Q000276:immunology; D016867:Immunocompromised Host; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D037181:Lectins, C-Type / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008172:Lung Diseases, Fungal / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D011014:Pneumonia / Q000276:immunology* / Q000382:microbiology; D054399:Receptors, CCR6 / Q000096:biosynthesis / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis; D015398:Signal Transduction; D051822:T Cell Transcription Factor 1 / Q000096:biosynthesis; D058504:Th17 Cells / Q000276:immunology*; D000099181:Dectin-1
chemical_list: D005657:Fungal Vaccines; D051538:Hepatocyte Nuclear Factor 1-alpha; D018664:Interleukin-12; D020381:Interleukin-17; D015850:Interleukin-6; D037181:Lectins, C-Type; D054399:Receptors, CCR6; D054367:Receptors, CXCR3; D011971:Receptors, Immunologic; D051822:T Cell Transcription Factor 1; D000099181:Dectin-1; C498126:CCR6 protein, mouse; C515188:Cxcr3 protein, mouse; C496488:Hnf1a protein, mouse; C451496:Klrg1 protein, mouse