Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation

<jats:p> Autophagy is a cell biological pathway affecting immune responses. In vitro, autophagy acts as a cell-autonomous defense against <jats:italic>Mycobacterium tuberculosis</jats:italic> , but its role in vivo is unknown. Here we show that autophagy plays a dual role against tuberculosis: antibacterial and anti-inflammatory. <jats:italic>M</jats:italic> . <jats:italic>tuberculosis</jats:italic> infection of Atg5 <jats:sup>fl/fl</jats:sup> LysM-Cre <jats:sup>+</jats:sup> 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 <jats:sup>fl/fl</jats:sup> LysM-Cre <jats:sup>+</jats:sup> 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 <jats:italic>M</jats:italic> . <jats:italic>tuberculosis</jats:italic> growth and damaging inflammation. </jats:p>