IL17A augments autophagy in Mycobacterium tuberculosis-infected monocytes from patients with active tuberculosis in association with the severity of the disease

• Published in: Autophagy Vol. 13; no. 7; pp. 1191 - 1204
• Main Authors: Tateosian, Nancy Liliana, Pellegrini, Joaquín Miguel, Amiano, Nicolás Oscar, Rolandelli, Agustín, Casco, Nicolás, Palmero, Domingo Juan, Colombo, María Isabel, García, Verónica Edith
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 03.07.2017
• Subjects: Autophagy; Basic Research Papers; Cells, Cultured; cytokines; Humans; IFNG; IL17A; immune response; Interferon-gamma - physiology; Interleukin-17 - physiology; Monocytes - immunology; Monocytes - microbiology; Mycobacterium tuberculosis; Mycobacterium tuberculosis - physiology; patients; Signal Transduction; tuberculosis; Tuberculosis - diagnosis; Tuberculosis - immunology; Tuberculosis - microbiology; autophagy; IFNG; Mycobacterium tuberculosis; immune response; patients; tuberculosis; cytokines; IL17A
• ISSN: 1554-8627; 1554-8635
• DOI: 10.1080/15548627.2017.1320636

During mycobacterial infection, macroautophagy/autophagy, a process modulated by cytokines, is essential for mounting successful host responses. Autophagy collaborates with human immune responses against Mycobacterium tuberculosis (Mt) in association with specific IFNG secreted against the pathogen. However, IFNG alone is not sufficient to the complete bacterial eradication, and other cytokines might be required. Actually, induction of Th1 and Th17 immune responses are required for protection against Mt. Accordingly, we showed that IL17A and IFNG expression in lymphocytes from tuberculosis patients correlates with disease severity. Here we investigate the role of IFNG and IL17A during autophagy in monocytes infected with Mt H37Rv or the mutant MtΔRD1. Patients with active disease were classified as high responder (HR) or low responder (LR) according to their T cell responses against Mt. IL17A augmented autophagy in infected monocytes from HR patients through a mechanism that activated MAPK1/ERK2-MAPK3/ERK1 but, during infection of monocytes from LR patients, IL17A had no effect on the autophagic response. In contrast, addition of IFNG to infected monocytes, increased autophagy by activating MAPK14/p38 α both in HR and LR patients. Interestingly, proteins codified in the RD1 region did not interfere with IFNG and IL17A autophagy induction. Therefore, in severe tuberculosis patients' monocytes, IL17A was unable to augment autophagy because of a defect in the MAPK1/3 signaling pathway. In contrast, both IFNG and IL17A increased autophagy levels in patients with strong immunity to Mt, promoting mycobacterial killing. Our findings might contribute to recognize new targets for the development of novel therapeutic tools to fight the pathogen.