Details

Autor(en) / Beteiligte

• Domingo-Gonzalez, Racquel
• Das, Shibali
• Griffiths, Kristin L
• Ahmed, Mushtaq
• Bambouskova, Monika
• Gopal, Radha
• Gondi, Suhas
• Muñoz-Torrico, Marcela
• Salazar-Lezama, Miguel A
• Cruz-Lagunas, Alfredo
• Jiménez-Álvarez, Luis
• Ramirez-Martinez, Gustavo
• Espinosa-Soto, Ramón
• Sultana, Tamanna
• Lyons-Weiler, James
• Reinhart, Todd A
• Arcos, Jesus
• de la Luz Garcia-Hernandez, Maria
• Mastrangelo, Michael A
• Al-Hammadi, Noor
• Townsend, Reid
• Balada-Llasat, Joan-Miquel
• Torrelles, Jordi B
• Kaplan, Gilla
• Horne, William
• Kolls, Jay K
• Artyomov, Maxim N
• Rangel-Moreno, Javier
• Zúñiga, Joaquín
• Khader, Shabaana A

Titel

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

Ist Teil von

• JCI insight, 2017-10, Vol.2 (19)

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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.