| Literature DB >> 25426782 |
Ana I Rovetta1, Delfina Peña, Rodrigo E Hernández Del Pino, Gabriela M Recalde, Joaquín Pellegrini, Fabiana Bigi, Rosa M Musella, Domingo J Palmero, Marisa Gutierrez, María I Colombo, Verónica E García.
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.Entities:
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
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Year: 2014 PMID： 25426782 PMCID： PMC4502660 DOI： 10.4161/15548627.2014.981791
Source DB: PubMed Journal: Autophagy ISSN： 1554-8627 Impact factor: 16.016