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Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation

2012; National Academy of Sciences; Volume: 109; Issue: 46 Linguagem: Inglês

10.1073/pnas.1210500109

1091-6490

Eliseo F. Castillo, Alexander Dekonenko, John Arko‐Mensah, Michael A. Mandell, Nicolas Dupont, Shanya Jiang, Monica Delgado-Vargas, Graham S. Timmins, Dhruva Bhattacharya, Hongliang Yang, Julie A. Hutt, C. Rick Lyons, Karen M. Dobos, Vojo Deretić,

Tuberculosis Research and Epidemiology

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 littermates resulted in increased bacillary burden and excessive pulmonary inflammation characterized by neutrophil infiltration and IL-17 response with increased IL-1α levels. Macrophages from uninfected Atg5 fl/fl LysM-Cre + mice displayed a cell-autonomous IL-1α 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.