PNAS Plus: Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation
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.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- November 2012
- DOI:
- 10.1073/pnas.1210500109
- Bibcode:
- 2012PNAS..109E3168C