Vaccinated C57BL/6 Mice Develop Protective and Memory T Cell Responses to Coccidioides posadasii Infection in the Absence of Interleukin-10

Abstract

High concentrations of lung tissue-associated interleukin-10 (IL-10), an anti-inflammatory and immunosuppressive cytokine, correlate with susceptibility of mice to Coccidioides spp. infection. In this study, we found that macrophages, dendritic cells, neutrophils, and both CD8(+) and CD4(+) T cells recruited to Coccidioides posadasii-infected lungs of nonvaccinated and vaccinated mice contributed to the production of IL-10. The major IL-10-producing leukocytes were CD8(+) T cells, neutrophils, and macrophages in lungs of nonvaccinated mice, while both Foxp3(+) and Foxp3(-) subsets of IL-10(+) CD4(+) T cells were significantly elevated in vaccinated mice. Profiles of the recruited leukocytes in lungs revealed that only CD4(+) T cells were significantly increased in IL-10(-/-) knockout mice compared to their wild-type counterparts. Furthermore, ex vivo recall assays showed that CD4(+) T cells isolated from vaccinated IL-10(-/-) mice compared to vaccinated wild-type mice produced significantly higher amounts of IL-2, gamma interferon (IFN-γ), IL-4, IL-6, and IL-17A in the presence of a coccidioidal antigen, indicating that IL-10 suppresses Th1, Th2, and Th17 immunity to Coccidioides infection. Analysis of absolute numbers of CD44(+) CD62L(-) CD4(+) T effector memory T cells (TEM) and IFN-γ- and IL-17A-producing CD4(+) T cells in the lungs of Coccidioides-infected mice correlated with better fungal clearance in nonvaccinated IL-10(-/-) mice than in nonvaccinated wild-type mice. Our results suggest that IL-10 suppresses CD4(+) T-cell immunity in nonvaccinated mice during Coccidioides infection but does not impede the development of a memory response nor exacerbate immunopathology of vaccinated mice over at least a 4-month period after the last immunization.