First Author | Castillo EF | Year | 2012 |
Journal | Proc Natl Acad Sci U S A | Volume | 109 |
Issue | 46 | Pages | E3168-76 |
PubMed ID | 23093667 | Mgi Jnum | J:191229 |
Mgi Id | MGI:5461274 | Doi | 10.1073/pnas.1210500109 |
Citation | Castillo EF, et al. (2012) Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation. Proc Natl Acad Sci U S A 109(46):E3168-76 |
abstractText | 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-1alpha levels. Macrophages from uninfected Atg5(fl/fl) LysM-Cre(+) mice displayed a cell-autonomous IL-1alpha 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. |