Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation
Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation
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DOI：
10.1073/pnas.1210500109
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发表时间：
2012-11-13
影响因子：
11.1
通讯作者：
Deretic, Vojo
中科院分区：
文献类型：
--
作者：
Castillo, Eliseo F.;Dekonenko, Alexander;Deretic, Vojo
自噬是影响免疫反应的一种细胞生物学途径。在体外，自噬起到了抵抗结核分枝杆菌的细胞自主防御作用，但它在体内的作用尚不清楚。在这里，我们展示了自噬在抗结核方面具有双重作用：抗菌和抗炎。结核分枝杆菌感染ATG5(fl/fl)LysM-Cre(+)小鼠相对于自噬熟练的小鼠，导致细菌负荷增加和以中性粒细胞浸润和IL-17反应为特征的过度肺部炎症，并伴随IL-1α水平的增加。未感染ATG5(f1/fl)LysM-Cre(+)小鼠的巨噬细胞表现出细胞自主的IL-1a高分泌表型，而T细胞在非特异性激活或用分枝杆菌抗原重新刺激时倾向于IL-17极化。因此，自噬在体内通过抑制结核分枝杆菌的生长和破坏炎症来发挥作用。
Autophagy is a cell biological pathway affecting immune responses. In vitro, autophagy acts as a cell-autonomous defense against Mycobacterium tuberculosis, but its role in vivo is unknown. Here we show that autophagy plays a dual role against tuberculosis: antibacterial and anti-inflammatory. M. tuberculosis infection of Atg5(fl/fl) LysM-Cre(+) mice relative to autophagy-proficient litter-mates resulted in increased bacillary burden and excessive pulmonary inflammation characterized by neutrophil infiltration and IL-17 response with increased IL-1 alpha levels. Macrophages from un-Infected Atg5(fl/fl) LysM-Cre(+) mice displayed a cell-autonomous IL-1a hypersecretion phenotype, whereas T cells showed propensity toward IL-17 polarization during nonspecific activation or upon restimulation with mycobacterial antigens. Thus, autophagy acts in vivo by suppressing both M. tuberculosis growth and damaging inflammation.