Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation

Departments of Molecular Genetics and Microbiology and Internal Medicine and College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 11/2012; 109(46):E3168-E3176. DOI: 10.1073/pnas.1210500109
Source: PubMed

ABSTRACT 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 Atg5fl/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 Atg5fl/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.

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