GM-CSF+ Tc17 cells mediate vaccine-immunity, but not immunopathology, against lethal fungal pneumonia under CD4+ T-cell lymphopenia
| Autor: | Srinivasu Mudalagiriyappa, Miranda Vieson, Som G Nanjappa |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 204:82.34-82.34 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.204.supp.82.34 |
| Popis: | Although opportunistic fungal infections are rising at alarming rates in immunocompromised individuals, there is no licensed vaccine available nor the clear understanding of the protective host responses. In a mouse model of fungal vaccine-immunity in CD4+ T-cell lymphopenia, we have previously shown that vaccine-induced IL-17A producing CD8+ T (Tc17) cells are necessary for controlling lethal fungal pneumonia. However, we found a significant number of Tc17 cells that co-expressed GM-CSF (>50%), but their role has been implicated as ‘pathogenic’ in autoimmune disorders. In this study, using state-of-the-art approaches, we found that GM-CSF +Tc17 cells are essential for vaccine-immunity against lethal fungal pneumonia without precipitating an adverse immunopathology. Induction of GM-CSF+Tc17 cells, following vaccination, required signaling from cytokines, IL-1 and IL-23, that promoted differentiation and proliferation of effectors. However, memory homeostasis of GM-CSF+Tc17 cells was mostly independent of IL-23. Following the lethal challenge by the pulmonary route, IL-23 was required for the GM-CSF+Tc17 cells responses, but not for their re-differentiation, and was necessary to mitigate the immunopathology of the lungs. Collectively, GM-CSF+Tc17 cells are required for vaccine-mediated immunity against lethal fungal pneumonia. |
| Databáze: | OpenAIRE |
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