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

Date

2014-01-22

Authors

Hung, Chiung-Yu
Castro-Lopez, Natalia
Cole, Garry T.

Journal Title

Journal ISSN

Volume Title

Publisher

American Society for Microbiology

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.

Description

Keywords

Coccidioides posadasii

Citation

Hung, C.-Y., Castro-Lopez, N., & Cole, G. T. (2014). Vaccinated C57BL/6 Mice Develop Protective and Memory T Cell Responses to Coccidioides posadasii Infection in the Absence of Interleukin-10. Infection and Immunity, 82(2), 903-913. doi:doi:10.1128/iai.01148-13

Department

Molecular Microbiology and Immunology