TNFRp75‐dependent immune regulation of alveolar macrophages and neutrophils during early Mycobacterium tuberculosis and Mycobacterium bovis BCG infection,Immunology

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TNFRp75‐dependent immune regulation of alveolar macrophages and neutrophils during early Mycobacterium tuberculosis and Mycobacterium bovis BCG infection
Immunology ( IF 4.9 ) Pub Date : 2020-10-06 , DOI: 10.1111/imm.13277
Avril Walters ₁ , Roanne Keeton ₁ , Antoinette Labuschagné ₁ , Nai-Jen Hsu ₁ , Muazzam Jacobs _{1,

2,

3}

Affiliation

TNF signalling through TNFRp55 and TNFRp75, and receptor shedding is important for immune activation and regulation. TNFRp75 deficiency leads to improved control of Mycobacterium tuberculosis (M. tuberculosis) infection, but the effects of early innate immune events in this process are unclear. We investigated the role of TNFRp75 on cell activation and apoptosis of alveolar macrophages and neutrophils during M. tuberculosis and M. bovis BCG infection. We found increased microbicidal activity against M. tuberculosis occurred independently of IFNy and NO generation, and displayed an inverse correlation with alveolar macrophages (AMs) apoptosis. Both M. tuberculosis and M. bovis BCG induced higher expression of MHC‐II in TNFRp75^−/− AMs; however, M bovis BCG infection did not alter AM apoptosis in the absence of TNFRp75. Pulmonary concentrations of CCL2, CCL3 and IL‐1β were increased in TNFRp75^−/− mice during M, bovis BCG infection, but had no effect on neutrophil responses. Thus, TNFRp75‐dependent regulation of mycobacterial replication is virulence dependent and occurs independently of early alveolar macrophage apoptosis and neutrophil responses.

中文翻译：

早期结核分枝杆菌和牛分枝杆菌 BCG 感染期间肺泡巨噬细胞和中性粒细胞的 TNFRp75 依赖性免疫调节

通过 TNFRp55 和 TNFRp75 的 TNF 信号传导和受体脱落对于免疫激活和调节很重要。TNFRp75 缺乏导致对结核分枝杆菌( M. tuberculosis )感染的控制得到改善，但早期先天免疫事件在此过程中的影响尚不清楚。我们研究了 TNFRp75 在M期间对肺泡巨噬细胞和中性粒细胞的细胞活化和凋亡的作用。结核病和M . 牛卡介苗感染。我们发现对M的杀菌活性增加。结核发生独立于 IFNγ 和 NO 的产生，并与肺泡巨噬细胞 (AMs) 凋亡呈负相关。两个M。结核病和M . bovis BCG 在 TNFRp75 ^-/- AMs中诱导更高的 MHC-II 表达；然而，在没有 TNFRp75 的情况下，牛支原体 BCG 感染不会改变 AM 细胞凋亡。在M、bovis期间，TNFRp75 ^-/-小鼠的肺中 CCL2、CCL3 和 IL-1β 浓度增加BCG 感染，但对中性粒细胞反应没有影响。因此，分枝杆菌复制的 TNFRp75 依赖性调节是毒力依赖性的，并且独立于早期肺泡巨噬细胞凋亡和中性粒细胞反应而发生。

更新日期：2020-10-06

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