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

• DOI: 10.1172/jci.insight.92973
• Publication Date: 2017-10-04T15:00:45Z
• Authors: Racquel Domingo-G...; Shibali Das; Kristin L. Griffiths; Mushtaq Ahmed; Monika Bambouskova; Radha Gopal; Suhas Gondi; Marcela Muñoz-Tor...; Miguel A. Salazar...; Alfredo Cruz-Lagunas; Luis Jiménez-Álvarez; Gustavo Ramirez-M...; Ramón Espinosa-Soto; Tamanna Sultana; James Lyons-Weiler; Todd A. Reinhart; Jesus Arcos; Maria de la Luz G...; Michael A. Mastra...; Noor Al-Hammadi; Reid Townsend; Joan-Miquel Balad...; Jordi B. Torrelles; Gilla Kaplan; William Horne; Jay K. Kolls; Maxim N. Artyomov; Javier Rangel-Moreno; Joaquín Zúñiga; Shabaana A. Khader
• Keywords: Hypoxia; Hypoxia-Inducible Factors

Mycobacterium tuberculosis (Mtb) is a global health threat, compounded by the emergence of drug-resistant strains. A hallmark pulmonary (TB) formation hypoxic necrotic granulomas, which upon disintegration, release infectious Mtb. Furthermore, granulomas are associated with increased disease severity and provide niche for However, host immune responses that promote development TB not well described. Using Mtb mouse model, we show loss virulence factors, such as phenolic glycolipids, decreases production proinflammatory cytokine IL-17 (also referred to IL-17A). negatively regulates limiting expression transcription factor hypoxia-inducible 1α (HIF1α). In human patients, HIF1α mRNA increased. Through genotyping association analyses in samples, identified link between single nucleotide polymorphism rs2275913 promoter (-197G/G), decreased stimulation cell wall. Together, our data highlight potentially novel role reducing TB.