Essential role for IL-27 receptor signaling in prevention of Th1-mediated immunopathology during malaria infection

The Journal of Immunology : Official Journal of the American Association of Immunologists
Emily Gwyer FindlayKevin N Couper

Abstract

Successful resolution of malaria infection requires induction of proinflammatory immune responses that facilitate parasite clearance; however, failure to regulate this inflammation leads to immune-mediated pathology. The pathways that maintain this immunological balance during malaria infection remain poorly defined. In this study, we demonstrate that IL-27R-deficient (WSX-1(-/-)) mice are highly susceptible to Plasmodium berghei NK65 infection, developing exacerbated Th1-mediated immune responses, which, despite highly efficient parasite clearance, lead directly to severe liver pathology. Depletion of CD4(+) T cells---but not CD8(+) T cells---prevented liver pathology in infected WSX-1(-/-) mice. Although WSX-1 signaling was required for optimal IL-10 production by CD4(+) T cells, administration of rIL-10 failed to ameliorate liver damage in WSX-1(-/-) mice, indicating that additional, IL-10-independent, protective pathways are modulated by IL-27R signaling during malaria infection. These data are the first to demonstrate the essential role of IL-27R signaling in regulating effector T cell function during malaria infection and reveal a novel pathway that might be amenable to manipulation by drugs or vaccines.

References

Nov 1, 1995·The Journal of Experimental Medicine·P R GalleL Runkel
Feb 16, 2002·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Q XuX M Zhang
May 8, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Atsunobu TakedaHiroki Yoshida
Jul 19, 2003·Clinical and Experimental Immunology·K Artavanis-TsakonasE M Riley
Nov 15, 2003·Immunity·Alejandro VillarinoChristopher A Hunter
Feb 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stefan PflanzRobert A Kastelein
Sep 10, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sadahiro KamiyaTakayuki Yoshimoto
Dec 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·John E PearlAndrea M Cooper
Mar 8, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christoph HölscherStefan Ehlers
Jun 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alejandro V VillarinoChristopher A Hunter
Jul 19, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Feng ZhouMark G Swain
Aug 6, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Toshiyuki OwakiTakayuki Yoshimoto
Dec 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alejandro V VillarinoChristopher A Hunter
Feb 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Toshiyuki OwakiTakayuki Yoshimoto
Aug 2, 2006·The Journal of Experimental Medicine·Stefan WirtzMarkus F Neurath
Aug 22, 2006·Immunobiology·Dominik RückerlChristoph Hölscher
Nov 23, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Toshiyuki OwakiTakayuki Yoshimoto
Feb 13, 2007·Annual Review of Immunology·Robert A KasteleinDaniel J Cua
Aug 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Denise C FitzgeraldAbdolmohamad Rostami
Nov 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sen WangHiroki Yoshida
Nov 13, 2007·Nature Immunology·Jason S StumhoferChristopher A Hunter
Feb 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marcel BattenNico Ghilardi
Apr 1, 2008·International Immunology·Alejandro V VillarinoChristopher A Hunter
Apr 22, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·George D Kalliolias, Lionel B Ivashkiv
Jun 19, 2008·The Journal of Infectious Diseases·Cory M Robinson, Gerard J Nau
Jan 24, 2009·Immunological Reviews·Hiroki YoshidaMiyazaki Yoshiyuki
Apr 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Caroline DiveuRobert A Kastelein
Sep 15, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Charles F AndersonDavid Sacks

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Citations

Dec 23, 2011·Journal of Biomedicine & Biotechnology·Mamoru NiikuraFumie Kobayashi
May 9, 2014·PLoS Pathogens·Francesca Diane M LiuAlf Hamann
Jun 4, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maria Teresa P de AquinoStephen A Stohlman
Jan 23, 2016·Advanced Pharmaceutical Bulletin·Fatemeh ZamaniMohammad Reza Aliparasti
Dec 15, 2015·FEMS Microbiology Reviews·Katrien DeroostPhilippe E Van den Steen
Apr 12, 2015·Annual Review of Immunology·Hiroki Yoshida, Christopher A Hunter
Oct 30, 2014·Frontiers in Immunology·Christian R EngwerdaPatrick T Bunn
Mar 31, 2017·The Journal of Experimental Medicine·Shoko KitadaKiyoshi Takeda
Feb 3, 2016·Trends in Immunology·Nathan D PennockRoss M Kedl
Feb 14, 2018·Clinical and Experimental Immunology·G W JonesS A Jones
Jul 31, 2013·Infection and Immunity·Shoichiro MineoFumie Kobayashi
Jan 15, 2016·PLoS Pathogens·Marcela Montes de OcaChristian R Engwerda
Mar 29, 2014·Parasite Immunology·S A RedpathG Perona-Wright
Aug 2, 2013·Journal of Leukocyte Biology·Markus Bosmann, Peter A Ward
Jun 5, 2020·Parasite Immunology·Katsuyuki Yui, Shin-Ichi Inoue
Dec 30, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ana Paula Freitas do RosárioJean Langhorne
Mar 19, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Qianqian ChengWeiqing Pan
Mar 29, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Emily Gwyer FindlayKevin N Couper
Nov 22, 2016·Frontiers in Immunology·Hideaki HasegawaTakayuki Yoshimoto
Apr 4, 2019·Nature Reviews. Immunology·Samarchith P KurupJohn T Harty
Feb 28, 2019·Frontiers in Immunology·Rajiv KumarChristian Engwerda
May 22, 2019·Journal of Immunology Research·Aneesh ThakurGregers Jungersen
Nov 5, 2019·Frontiers in Immunology·Kelvin M KimenyiLynette Isabella Ochola-Oyier
Aug 21, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ana Villegas-MendezKevin N Couper

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