Mycobacterial hypersensitivity pneumonitis requires TLR9-MyD88 in lung CD11b+CD11c+cells
Mycobacterial hypersensitivity pneumonitis requires TLR9-MyD88 in lung CD11b+CD11c+cells
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DOI：
10.1183/09031936.00177110
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发表时间：
2011-09-01
影响因子：
24.3
通讯作者：
Nukiwa, T.
中科院分区：
文献类型：
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作者：
Daito, H.;Kikuchi, T.;Nukiwa, T.
分枝杆菌是过敏性肺炎（HP）最常见的原因之一，但关于分枝杆菌HP（热浴肺）中微生物的感染力的参与仍然存在争议。本研究旨在建立小鼠热水浴缸肺模型，以阐明其病理生理学。小鼠鼻内暴露于来自热水浴缸肺（HP株）或慢性肺部感染（非HP株）患者的福尔马林灭活的鸟分支杆菌，并评估支气管肺泡灌洗液和肺组织的过敏性炎症。死亡M.禽HP菌株而非非HP菌株在野生型小鼠中引起显著的HP样肺部炎症。尽管在缺乏CD 4或CD 8的小鼠中诱导了炎症，但在缺乏髓样分化因子（MyD）88或Toll样受体（TLR）9的小鼠中阻止了HP样应答的诱导。培养的肺CD 11 c+细胞对M.用野生型小鼠的肺CD 11 c+细胞重建TLR 9-/-小鼠，恢复了炎症反应。进一步的研究表明，肺暴露于M。本研究结果表明，热浴肺的发生是通过结核分枝杆菌介导的TLR 9-MyD 88信号转导途径，而与结核分枝杆菌的感染能力无关。
Mycobacteria are among the most common causes of hypersensitivity pneumonitis (HP), but controversy persists with regard to the involvement of the infectious potency of the organism in mycobacterial HP (hot tub lung). This study aimed to establish a mouse model of hot tub lung to clarify its pathophysiology.Mice were exposed intranasally to formalin-killed Mycobacterium avium from a patient with hot tub lung (HP strain) or chronic pulmonary infection (non-HP strain), and bronchoalveolar lavage fluids and lung tissues were evaluated for allergic inflammation.Dead M. avium HP strain, but not non-HP strain, elicited marked HP-like pulmonary inflammation in wild-type mice. Although the inflammation was induced in mice lacking CD4 or CD8, the induction of HP-like responses was prevented in mice lacking myeloid differentiation factor (MyD)88 or Toll-like receptor (TLR)9. Cultured lung CD11c+ cells responded to M. avium in a TLR9-dependent manner, and reconstitution of TLR9-/- mice with lung CD11c+ cells from wildtype mice restored the inflammatory responses. Further investigation revealed that pulmonary exposure to M. avium HP strain increased the number of lung CD11b+ CD11c+ cells (dendritic cells) through TLR9 signalling.Our results provide evidence that hot tub lung develops via the mycobacterial engagement of TLR9-MyD88 signalling in lung CD11b+ dendritic cells independent of the mycobacterial infectious capacity.