HIF-1α hampers dendritic cell function and Th1 generation during chronic visceral leishmaniasis

Scientific Reports
Akil HammamiSimona Stäger

Abstract

Inflammation, although responsible for controlling infection, is often associated with the pathogenesis of chronic diseases. Leishmania donovani, the causative agent of visceral leishmaniasis, induces a strong inflammatory response that leads to splenomegaly and ultimately immune suppression. Inflamed tissues are typically characterized by low levels of oxygen, a microenvironment that triggers the hypoxia-inducible transcription factor 1α (HIF-1α). Although HIF-1α plays an integral role in dendritic cell function, its involvement in the generation of protective Th1 responses against Leishmania has not yet been studied. Here we demonstrate that HIF-1α inhibits IL-12 production in dendritic cells, limiting therefore Th1 cell development. Indeed, depletion of HIF-1α in CD11c+ cells resulted in higher and sustained expression of IL-12 and complete abrogation of IL-10. Moreover, CD11c-specific HIF-1α-deficient mice showed higher frequencies of IFN-γ-producing CD4 T cells in the spleen and bone marrow and, consequently, a significantly reduced parasite burden in both organs. Taken together, our results suggest that HIF-1α expression in dendritic cells largely contributes to the establishment of persistent Leishmania infection and may...Continue Reading

References

Jun 22, 1999·The Journal of Experimental Medicine·T OhtekiS Koyasu
Mar 12, 2003·Cell·Thorsten CramerRandall S Johnson
Sep 14, 2004·Immunological Reviews·Paul M KayeChristian R Engwerda
Apr 6, 2005·The Journal of Experimental Medicine·Jason K WhitmireJ Lindsay Whitton
Jul 12, 2005·The Journal of Clinical Investigation·Carole PeyssonnauxRandall S Johnson
Apr 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Manabu AtoPaul M Kaye
Aug 11, 2007·Trends in Immunology·Susanne Nylén, David Sacks
Feb 24, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhengguo XiaoMatthew F Mescher
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Dilini RanatungaJay H Bream
Jan 18, 2011·Nature Immunology·Thomas KrausgruberIrina A Udalova
Apr 27, 2011·Scandinavian Journal of Immunology·A DegrossoliS Giorgio
Jul 13, 2011·Nature Reviews. Microbiology·Paul Kaye, Phillip Scott
Jan 11, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Guillermo Arango DuqueAlbert Descoteaux
Aug 16, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nicholas P GoplenEmma Teixeiro
May 31, 2017·Nature Communications·Simon J LawlessDavid K Finlay
Oct 4, 2017·Nature Reviews. Immunology·Cormac T Taylor, Sean P Colgan

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Citations

Nov 6, 2018·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·C L StothersJ K Bohannon
Oct 12, 2018·Biochemical Society Transactions·Abel AngMargreet C M Vissers
Aug 16, 2019·Physiological Reviews·Carla Riera-DomingoMassimiliano Mazzone
Apr 30, 2019·Frontiers in Immunology·Mohammad AsadNahid Ali
Mar 16, 2019·Frontiers in Immunology·Rafael TibúrcioCláudia Brodskyn
Feb 11, 2020·Frontiers in Immunology·Linh Thuy MaiSimona Stäger
Oct 6, 2020·Pathogens and Disease·Mayra A Rodríguez-SerratoAlberto Yairh Limón-Flores
Dec 19, 2019·Microorganisms·Camila Dos Santos Meira, Lashitew Gedamu
Feb 2, 2021·Obesity Medicine·Antoine AbdelMassihJianping Ye
Aug 14, 2020·Microorganisms·Nnamdi M IkeoguJude E Uzonna
Aug 28, 2020·Cell Metabolism·Anne F McGettrick, Luke A J O'Neill
Jun 26, 2021·Trends in Immunology·Laís P PralMarco A R Vinolo

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Methods Mentioned

BETA
PCR
transgenic
flow cytometry

Software Mentioned

FACSDiva
flowjo

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