title: IFNG-mediated immune responses enhance autophagy against Mycobacterium tuberculosis antigens in patients with active tuberculosis.
abstract: Protective immunity against Mycobacterium tuberculosis (Mtb) requires IFNG. Besides, IFNG-mediated induction of autophagy suppresses survival of virulent Mtb in macrophage cell lines. We investigated the contribution of autophagy to the defense against Mtb antigen (Mtb-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 Mtb-Ag; and low responders (LR) when patients showed weak or no T cell responses to Mtb-Ag. The highest autophagy levels were detected in HD cells whereas the lowest quantities were observed in LR patients. Interestingly, upon Mtb-Ag stimulation, we detected a positive correlation between IFNG and MAP1LC3B-II/LC3-II levels. Actually, blockage of Mtb-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 Mtb in close association with specific IFNG secreted against the pathogen.
authors.affiliation: a Departamento de Química Biológica; Facultad de Ciencias Exactas y Naturales; Universidad de Buenos Aires (UBA) ; Buenos Aires , Argentina.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Rovetta
authors.forename: Delfina
authors.initials: D
authors.lastname: Peña
authors.forename: Rodrigo E
authors.initials: RE
authors.lastname: Hernández Del Pino
authors.forename: Gabriela M
authors.initials: GM
authors.lastname: Recalde
authors.forename: Joaquín
authors.initials: J
authors.lastname: Pellegrini
authors.forename: Fabiana
authors.initials: F
authors.lastname: Bigi
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Musella
authors.forename: Domingo J
authors.initials: DJ
authors.lastname: Palmero
authors.forename: Marisa
authors.initials: M
authors.lastname: Gutierrez
authors.forename: María I
authors.initials: MI
authors.lastname: Colombo
authors.forename: Verónica E
authors.initials: VE
authors.lastname: García
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology*; D001343:Autophagy / Q000187:drug effects* / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D014376:Tuberculosis / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; C072681:Mycobacterium tuberculosis antigens; D007371:Interferon-gamma
keywords: AG, antigen; ATG, autophagy-related; FBS, fetal bovine serum; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GTP, guanosine triphosphate; HD, healthy donors; HR TB, high-responder tuberculosis patient; IFNG; IFNG, interferon gamma; IL, Interleukin; LC3, microtubule-associated protein 1A/1B-light chain 3; LR TB, low-responder tuberculosis patients; Mtb-Ag, Mycobacterium tuberculosis antigen; PBMC, peripheral blood mononuclear cells; PBS, phosphate-buffered saline; SLAM, signaling lymphocytic activation molecule; TB, tuberculosis; Th, T helper; autophagy; cytokines; defense; immune response; mAb, monoclonal antibody; patients; rIFNG, recombinant IFNG; tuberculosis