Interleukin-17 limits hypoxia-inducible factor 1α and development of hypoxic granulomas during tuberculosis.

Autor:	Domingo-Gonzalez R; Department of Molecular Microbiology and., Das S; Department of Molecular Microbiology and., Griffiths KL; Department of Molecular Microbiology and., Ahmed M; Department of Molecular Microbiology and., Bambouskova M; Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA., Gopal R; Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA., Gondi S; Department of Molecular Microbiology and., Muñoz-Torrico M; Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico., Salazar-Lezama MA; Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico., Cruz-Lagunas A; Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico., Jiménez-Álvarez L; Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico., Ramirez-Martinez G; Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico., Espinosa-Soto R; Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico., Sultana T; Bioinformatics Analysis Core, Genomics and Proteomics Core Laboratories, and., Lyons-Weiler J; Bioinformatics Analysis Core, Genomics and Proteomics Core Laboratories, and., Reinhart TA; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Arcos J; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, USA., de la Luz Garcia-Hernandez M; Cardiovascular Research Institute, Department of Medicine, University of Rochester Medical Center, Rochester, New York, USA., Mastrangelo MA; Cardiovascular Research Institute, Department of Medicine, University of Rochester Medical Center, Rochester, New York, USA., Al-Hammadi N; Division of Biostatistics and., Townsend R; Proteomics Shared Resource, Washington University in St. Louis, St. Louis, Missouri, USA., Balada-Llasat JM; Department of Pathology, College of Medicine, The Ohio State University, Columbus, Ohio, USA., Torrelles JB; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, USA., Kaplan G; Public Health Research Institute Center, New Jersey Medical School-Rutgers, State University of New Jersey, Newark, New Jersey, USA., Horne W; Richard King Mellon Institute for Pediatric Research, Department of Pediatrics and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Kolls JK; Richard King Mellon Institute for Pediatric Research, Department of Pediatrics and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Artyomov MN; Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA., Rangel-Moreno J; Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, New York, USA., Zúñiga J; Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico., Khader SA; Department of Molecular Microbiology and.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2017 Oct 05; Vol. 2 (19). Date of Electronic Publication: 2017 Oct 05.
DOI:	10.1172/jci.insight.92973
Abstrakt:	Mycobacterium tuberculosis (Mtb) is a global health threat, compounded by the emergence of drug-resistant strains. A hallmark of pulmonary tuberculosis (TB) is the formation of hypoxic necrotic granulomas, which upon disintegration, release infectious Mtb. Furthermore, hypoxic necrotic granulomas are associated with increased disease severity and provide a niche for drug-resistant Mtb. However, the host immune responses that promote the development of hypoxic TB granulomas are not well described. Using a necrotic Mtb mouse model, we show that loss of Mtb virulence factors, such as phenolic glycolipids, decreases the production of the proinflammatory cytokine IL-17 (also referred to as IL-17A). IL-17 production negatively regulates the development of hypoxic TB granulomas by limiting the expression of the transcription factor hypoxia-inducible factor 1α (HIF1α). In human TB patients, HIF1α mRNA expression is increased. Through genotyping and association analyses in human samples, we identified a link between the single nucleotide polymorphism rs2275913 in the IL-17 promoter (-197G/G), which is associated with decreased IL-17 production upon stimulation with Mtb cell wall. Together, our data highlight a potentially novel role for IL-17 in limiting the development of hypoxic necrotic granulomas and reducing disease severity in TB.
Databáze:	MEDLINE
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