Involvement of IL‐17A‐producing TCR γδ T cells in late protective immunity against pulmonary Mycobacterium tuberculosis infection

Interleukin (IL)‐17A is a cytokine originally reported to induce neutrophil‐mediated inflammation and anti‐microbial activity. The CD4 + T cells, which produce IL‐17A, have been well characterized as Th17 cells. On the other hand, IL‐17A‐producing TCR γδ + T cells have been reported to participate in the immune response at an early stage of infection with Listeria monocytogenes and Mycobacterium bovis in mice. However, the involvement of IL‐17A in protective immunity was not clearly demonstrated in the chronic stage of M. tuberculosis ‐infected mice. Methods We analyzed role of IL‐17A in host defense against chronically infected M. tuberculosis using IL‐17A KO mice. Results We found that TCR γδ + T cells are a primary source of IL‐17A, but that mycobacterial antigen‐specific Th17 cells were hardly detected even at the chronic stage of M. tuberculosis infection. IL‐17A‐deficient mice showed a decreased survival rate, and increased bacterial burden in the lungs after the infection when compared to the wild‐type mice. Furthermore, a histological analysis showed an impaired granuloma formation in the infected lungs of IL‐17A‐deficient mice, which was considered to be due to a decrease of IFN‐γ and TNF at the chronic stage. Conclusion Our data suggest that the IL‐17A‐producing TCR γδ + T cells, rather than the Th17 cells, in the infected lungs are an indispensable source of protective immunity against M. tuberculosis infection.