IFNG-mediated immune responses enhance autophagy against <i>Mycobacterium tuberculosis</i> antigens in patients with active tuberculosis

Protective immunity against <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) requires IFNG. Besides, IFNG-mediated induction of autophagy suppresses survival of virulent <i>Mtb</i> in macrophage cell lines. We investigated the contribution of autophagy to the defense against <i>Mtb</i> antigen (<i>Mtb</i>-Ag) in cells from tuberculosis patients and healthy donors (HD). Patients were classified as high responders (HR) if their T cells produced significant IFNG against <i>Mtb</i>-Ag; and low responders (LR) when patients showed weak or no T cell responses to <i>Mtb</i>-Ag. The highest autophagy levels were detected in HD cells whereas the lowest quantities were observed in LR patients. Interestingly, upon <i>Mtb-</i>Ag stimulation, we detected a positive correlation between IFNG and MAP1LC3B-II/LC3-II levels. Actually, blockage of <i>Mtb</i>-Ag-induced IFNG markedly reduced autophagy in HR patients whereas addition of limited amounts of IFNG significantly increased autophagy in LR patients. Therefore, autophagy collaborates with human immune responses against <i>Mtb</i> in close association with specific IFNG secreted against the pathogen.