Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation

作者：Castillo Eliseo F; Dekonenko Alexander; Arko Mensah John; Mandell Michael A; Dupont Nicolas; Jiang Shanya; Delgado Vargas Monica; Timmins Graham S; Bhattacharya Dhruva; Yang Hongliang; Hutt Julie; Lyons C Rick; Dobos Karen M; Deretic Vojo^*

来源：Proceedings of the National Academy of Sciences, 2012, 109(46): E3168-E3176.

DOI：10.1073/pnas.1210500109

• Th17 response
• calpain
• inflammasome
• macrophage

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.

• 出版日期2012-11-13