IL-17 is a cytokine that induces neutrophil-mediated inflammation, but its role in protective immunity against intracellular bacterial infection remains unclear. In the present study, we demonstrate that IL-17 is an important cytokine not only in the early neutrophil-mediated inflammatory response, but also in T cell-mediated IFN-γ production and granuloma formation in response to pulmonary infection by Mycobacterium bovis bacille Calmette-Guérin (BCG). IL-17 expression in the BCG-infected lung was detected from the first day after infection and the expression depended on IL-23. Our observations indicated that γδ T cells are a primary source of IL-17. Lung-infiltrating T cells of IL-17-deficient mice produced less IFN-γ in comparison to those from wild-type mice 4 wk after BCG infection. Impaired granuloma formation was also observed in the infected lungs of IL-17-deficient mice, which is consistent with the decreased delayed-type hypersensitivity response of the infected mice against mycobacterial Ag. These data suggest that IL-17 is an important cytokine in the induction of optimal Th1 response and protective immunity against mycobacterial infection.

Introduction: 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.

Streptococcus pneumoniae is an important causative organism of respiratory tract infections. Although periodontal bacteria have been shown to influence respiratory infections such as aspiration pneumonia, the synergistic effect of S. pneumoniae and Porphyromonas gingivalis, a periodontopathic bacterium, on pneumococcal infections is unclear. To investigate whether P. gingivalis accelerates pneumococcal infections, we tested the effects of inoculating P. gingivalis culture supernatant (PgSup) into S. pneumoniae-infected mice. Mice were intratracheally injected with S. pneumoniae and PgSup to induce pneumonia, and lung histopathological sections and the absolute number and frequency of neutrophils and macrophages in the lung were analyzed. Proinflammatory cytokine/chemokine expression was examined by qPCR and ELISA. Inflammatory cell infiltration was observed in S. pneumoniae-infected mice and S. pnemoniae and PgSup mixed-infected mice, and mixed-infected mice showed more pronounced inflammation in lung. The ratios of monocytes/macrophages and neutrophils were not significantly different between the lungs of S. pneumoniae-infected mice and those of mixed-infected mice. PgSup synergistically increased TNF-α expression/production and IL-17 production compared with S. pneumoniae infection alone. We demonstrated that PgSup enhanced inflammation in pneumonia caused by S. pneumoniae, suggesting that virulence factors produced by P. gingivalis are involved in the exacerbation of respiratory tract infections such as aspiration pneumonia.

未だに世界中の人々を死に至らしめる最も大きな原因は感染症であり、病原性マイコバクテリアの代表である結核菌の感染も再び猛威を拡げ、感染症研究に大きな期待が掛けられている。結核菌感染症のなかでも特に肺結核はその発症頻度が高く、しばしば致命的な疾患に陥るにもかかわらず、肺における感染防御メカニズムは不明瞭な点が多い。この結核菌に対する免疫監視メカニズムと結核菌の病原因子の相互作用を理解し、結核菌感染症における免疫応答の分子基盤を整理および再構築することが、免疫制御による結核の予防ならびに治療法の開発に繋がると考えられる。本稿では、結核菌感染症における病原体側あるいは宿主側の視点からの感染制御メカニズムを概説すると共に、最近注目されているIL-17A/IL-23系の役割について解説する。