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

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Reduction of the lesion size in the lungs of IL‐17A KO mice after M. tuberculosis infection. Wild‐type C57BL/6 or IL‐17A KO mice were inoculated i.t. with M. tuberculosis H37Rv. The mice were sacrificed 30, 60, and 120 days after infection, and formalin‐fixed sections were stained with hematoxylin and eosin. Representative lung tissue specimens from the wild‐type C57BL/6 mice (left panel) and the IL‐17A KO mice (right panel) are shown. Magnification, ×40 (A), ×400 (B).
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iid3121-fig-0002: Reduction of the lesion size in the lungs of IL‐17A KO mice after M. tuberculosis infection. Wild‐type C57BL/6 or IL‐17A KO mice were inoculated i.t. with M. tuberculosis H37Rv. The mice were sacrificed 30, 60, and 120 days after infection, and formalin‐fixed sections were stained with hematoxylin and eosin. Representative lung tissue specimens from the wild‐type C57BL/6 mice (left panel) and the IL‐17A KO mice (right panel) are shown. Magnification, ×40 (A), ×400 (B).

Mentions: We previously reported that mature granuloma formation is impaired in the lung of the IL‐17A KO mice infected with M. bovis BCG 9, 10. However, it was not clear whether the defect impaired the pulmonary granuloma formation at the chronic stage of M. tuberculosis infection. To address this issue, we examined the histological changes in the lungs after i.t. infection with M. tuberculosis (Fig. 2). Although mycobacterial infection induced histopathological changes in the lungs of both the wild‐type C57BL/6 and IL‐17A KO mice, the granuloma number and size were smaller in IL‐17A KO mice than in wild‐type C57BL/6 mice (Fig. 2A). Furthermore, the granulomas in the lungs of IL‐17A KO mice were less densely packed with mononuclear cells compared to those of wild‐type C57BL/6 mice (Fig. 2B). These data indicate that IL‐17A is important in granuloma formation during M. tuberculosis infection.


Involvement of IL ‐ 17A ‐ producing TCR γ δ T cells in late protective immunity against pulmonary Mycobacterium tuberculosis infection
Reduction of the lesion size in the lungs of IL‐17A KO mice after M. tuberculosis infection. Wild‐type C57BL/6 or IL‐17A KO mice were inoculated i.t. with M. tuberculosis H37Rv. The mice were sacrificed 30, 60, and 120 days after infection, and formalin‐fixed sections were stained with hematoxylin and eosin. Representative lung tissue specimens from the wild‐type C57BL/6 mice (left panel) and the IL‐17A KO mice (right panel) are shown. Magnification, ×40 (A), ×400 (B).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5134718&req=5

iid3121-fig-0002: Reduction of the lesion size in the lungs of IL‐17A KO mice after M. tuberculosis infection. Wild‐type C57BL/6 or IL‐17A KO mice were inoculated i.t. with M. tuberculosis H37Rv. The mice were sacrificed 30, 60, and 120 days after infection, and formalin‐fixed sections were stained with hematoxylin and eosin. Representative lung tissue specimens from the wild‐type C57BL/6 mice (left panel) and the IL‐17A KO mice (right panel) are shown. Magnification, ×40 (A), ×400 (B).
Mentions: We previously reported that mature granuloma formation is impaired in the lung of the IL‐17A KO mice infected with M. bovis BCG 9, 10. However, it was not clear whether the defect impaired the pulmonary granuloma formation at the chronic stage of M. tuberculosis infection. To address this issue, we examined the histological changes in the lungs after i.t. infection with M. tuberculosis (Fig. 2). Although mycobacterial infection induced histopathological changes in the lungs of both the wild‐type C57BL/6 and IL‐17A KO mice, the granuloma number and size were smaller in IL‐17A KO mice than in wild‐type C57BL/6 mice (Fig. 2A). Furthermore, the granulomas in the lungs of IL‐17A KO mice were less densely packed with mononuclear cells compared to those of wild‐type C57BL/6 mice (Fig. 2B). These data indicate that IL‐17A is important in granuloma formation during M. tuberculosis infection.

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus