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

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....

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Autores principales:	Tateosian, N.L., Pellegrini, J.M., Amiano, N.O., Rolandelli, A., Casco, N., Palmero, D.J., Colombo, M.I., García, V.E.
Formato:	JOUR
Materias:	autophagy cytokines IFNG IL17A immune response Mycobacterium tuberculosis patients tuberculosis BCG vaccine CD14 antigen gamma interferon interleukin 17 interleukin 17 receptor interleukin 17 receptor A mitogen activated protein kinase 1 mitogen activated protein kinase 14 mitogen activated protein kinase 3 phosphatidylinositol 3 kinase tuberculostatic agent unclassified drug IFNG protein, human IL17A protein, human adherent cell Article autophagosome bacterial genome bacterial growth bactericidal activity controlled study disease classification disease severity enzyme activation human human cell intracellular signaling lung tuberculosis lysosome monocyte peripheral blood mononuclear cell phagosome protein phosphorylation upregulation cell culture immunology microbiology physiology signal transduction Autophagy Cells, Cultured Humans Interferon-gamma Interleukin-17 Monocytes Signal Transduction Tuberculosis
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_15548627_v13_n7_p1191_Tateosian
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_15548627_v13_n7_p1191_Tateosian
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spelling	todo:paper_15548627_v13_n7_p1191_Tateosian2023-10-03T16:25:34Z IL17A augments autophagy in Mycobacterium tuberculosis-infected monocytes from patients with active tuberculosis in association with the severity of the disease Tateosian, N.L. Pellegrini, J.M. Amiano, N.O. Rolandelli, A. Casco, N. Palmero, D.J. Colombo, M.I. García, V.E. autophagy cytokines IFNG IL17A immune response Mycobacterium tuberculosis patients tuberculosis BCG vaccine CD14 antigen gamma interferon interleukin 17 interleukin 17 receptor interleukin 17 receptor A mitogen activated protein kinase 1 mitogen activated protein kinase 14 mitogen activated protein kinase 3 phosphatidylinositol 3 kinase tuberculostatic agent unclassified drug gamma interferon IFNG protein, human IL17A protein, human interleukin 17 adherent cell Article autophagosome autophagy bacterial genome bacterial growth bactericidal activity controlled study disease classification disease severity enzyme activation human human cell intracellular signaling lung tuberculosis lysosome monocyte Mycobacterium tuberculosis peripheral blood mononuclear cell phagosome protein phosphorylation upregulation cell culture immunology microbiology monocyte Mycobacterium tuberculosis physiology signal transduction tuberculosis Autophagy Cells, Cultured Humans Interferon-gamma Interleukin-17 Monocytes Mycobacterium tuberculosis Signal Transduction Tuberculosis 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. © 2017 Taylor & Francis. Fil:Amiano, N.O. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:García, V.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_15548627_v13_n7_p1191_Tateosian
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	autophagy cytokines IFNG IL17A immune response Mycobacterium tuberculosis patients tuberculosis BCG vaccine CD14 antigen gamma interferon interleukin 17 interleukin 17 receptor interleukin 17 receptor A mitogen activated protein kinase 1 mitogen activated protein kinase 14 mitogen activated protein kinase 3 phosphatidylinositol 3 kinase tuberculostatic agent unclassified drug gamma interferon IFNG protein, human IL17A protein, human interleukin 17 adherent cell Article autophagosome autophagy bacterial genome bacterial growth bactericidal activity controlled study disease classification disease severity enzyme activation human human cell intracellular signaling lung tuberculosis lysosome monocyte Mycobacterium tuberculosis peripheral blood mononuclear cell phagosome protein phosphorylation upregulation cell culture immunology microbiology monocyte Mycobacterium tuberculosis physiology signal transduction tuberculosis Autophagy Cells, Cultured Humans Interferon-gamma Interleukin-17 Monocytes Mycobacterium tuberculosis Signal Transduction Tuberculosis
spellingShingle	autophagy cytokines IFNG IL17A immune response Mycobacterium tuberculosis patients tuberculosis BCG vaccine CD14 antigen gamma interferon interleukin 17 interleukin 17 receptor interleukin 17 receptor A mitogen activated protein kinase 1 mitogen activated protein kinase 14 mitogen activated protein kinase 3 phosphatidylinositol 3 kinase tuberculostatic agent unclassified drug gamma interferon IFNG protein, human IL17A protein, human interleukin 17 adherent cell Article autophagosome autophagy bacterial genome bacterial growth bactericidal activity controlled study disease classification disease severity enzyme activation human human cell intracellular signaling lung tuberculosis lysosome monocyte Mycobacterium tuberculosis peripheral blood mononuclear cell phagosome protein phosphorylation upregulation cell culture immunology microbiology monocyte Mycobacterium tuberculosis physiology signal transduction tuberculosis Autophagy Cells, Cultured Humans Interferon-gamma Interleukin-17 Monocytes Mycobacterium tuberculosis Signal Transduction Tuberculosis Tateosian, N.L. Pellegrini, J.M. Amiano, N.O. Rolandelli, A. Casco, N. Palmero, D.J. Colombo, M.I. García, V.E. IL17A augments autophagy in Mycobacterium tuberculosis-infected monocytes from patients with active tuberculosis in association with the severity of the disease
topic_facet	autophagy cytokines IFNG IL17A immune response Mycobacterium tuberculosis patients tuberculosis BCG vaccine CD14 antigen gamma interferon interleukin 17 interleukin 17 receptor interleukin 17 receptor A mitogen activated protein kinase 1 mitogen activated protein kinase 14 mitogen activated protein kinase 3 phosphatidylinositol 3 kinase tuberculostatic agent unclassified drug gamma interferon IFNG protein, human IL17A protein, human interleukin 17 adherent cell Article autophagosome autophagy bacterial genome bacterial growth bactericidal activity controlled study disease classification disease severity enzyme activation human human cell intracellular signaling lung tuberculosis lysosome monocyte Mycobacterium tuberculosis peripheral blood mononuclear cell phagosome protein phosphorylation upregulation cell culture immunology microbiology monocyte Mycobacterium tuberculosis physiology signal transduction tuberculosis Autophagy Cells, Cultured Humans Interferon-gamma Interleukin-17 Monocytes Mycobacterium tuberculosis Signal Transduction Tuberculosis
description	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. © 2017 Taylor & Francis.
format	JOUR
author	Tateosian, N.L. Pellegrini, J.M. Amiano, N.O. Rolandelli, A. Casco, N. Palmero, D.J. Colombo, M.I. García, V.E.
author_facet	Tateosian, N.L. Pellegrini, J.M. Amiano, N.O. Rolandelli, A. Casco, N. Palmero, D.J. Colombo, M.I. García, V.E.
author_sort	Tateosian, N.L.
title	IL17A augments autophagy in Mycobacterium tuberculosis-infected monocytes from patients with active tuberculosis in association with the severity of the disease
title_short	IL17A augments autophagy in Mycobacterium tuberculosis-infected monocytes from patients with active tuberculosis in association with the severity of the disease
title_full	IL17A augments autophagy in Mycobacterium tuberculosis-infected monocytes from patients with active tuberculosis in association with the severity of the disease
title_fullStr	IL17A augments autophagy in Mycobacterium tuberculosis-infected monocytes from patients with active tuberculosis in association with the severity of the disease
title_full_unstemmed	IL17A augments autophagy in Mycobacterium tuberculosis-infected monocytes from patients with active tuberculosis in association with the severity of the disease
title_sort	il17a augments autophagy in mycobacterium tuberculosis-infected monocytes from patients with active tuberculosis in association with the severity of the disease
url	http://hdl.handle.net/20.500.12110/paper_15548627_v13_n7_p1191_Tateosian
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IL17A augments autophagy in Mycobacterium tuberculosis-infected monocytes from patients with active tuberculosis in association with the severity of the disease

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