Plasmodium DNA-mediated TLR9 activation of T-bet+ B cells contributes to autoimmune anaemia during malaria

Nature Communications
J Rivera-CorreaA Rodriguez

Abstract

Infectious pathogens contribute to the development of autoimmune disorders, but the mechanisms connecting these processes are incompletely understood. Here we show that Plasmodium DNA induces autoreactive responses against erythrocytes by activating a population of B cells expressing CD11c and the transcription factor T-bet, which become major producers of autoantibodies that promote malarial anaemia. Additionally, we identify parasite DNA-sensing through Toll-like receptor 9 (TLR9) along with inflammatory cytokine receptor IFN-γ receptor (IFN-γR) as essential signals that synergize to promote the development and appearance of these autoreactive T-bet+ B cells. The lack of any of these signals ameliorates malarial anaemia during infection in a mouse model. We also identify both expansion of T-bet+ B cells and production of anti-erythrocyte antibodies in ex vivo cultures of naive human peripheral blood mononuclear cells (PBMC) exposed to P. falciprum infected erythrocyte lysates. We propose that synergistic TLR9/IFN-γR activation of T-bet+ B cells is a mechanism underlying infection-induced autoimmune-like responses.

References

Jan 1, 1983·Transactions of the Royal Society of Tropical Medicine and Hygiene·C Daniel-RibeiroM Gentilini
Jun 1, 1997·Clinical and Experimental Immunology·M G SalmonJ H Playfair
Sep 7, 2000·Acta Tropica·C T Daniel-Ribeiro, G Zanini
Dec 29, 2000·Nature·H HemmiS Akira
Nov 16, 2001·Annals of the New York Academy of Sciences·S GalJ S Wainscoat
Nov 22, 2001·The American Journal of Tropical Medicine and Hygiene·R N PriceN J White
Mar 27, 2002·Nature Reviews. Immunology·Ken Shortman, Yong-Jun Liu
Apr 12, 2002·Nature·Elizabeth A LeadbetterAnn Marshak-Rothstein
Apr 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·Stanford L PengLaurie H Glimcher
Feb 22, 2003·Immunity·Hui LiMartin Weigert
Mar 2, 2005·The Journal of Experimental Medicine·Sergey YurasovMichel C Nussenzweig
Sep 26, 2007·Annals of the New York Academy of Sciences·Tatiana BerlinYehuda Shoenfeld
Jun 20, 2008·Nature Immunology·Jean LanghorneKevin Marsh
Aug 1, 2009·Trends in Immunology·Shaye KivityYehuda Shoenfeld
Dec 17, 2009·Hematology·Kasturi Haldar, Narla Mohandas
Jan 18, 2011·International Reviews of Immunology·Himanshu KumarShizuo Akira
Feb 2, 2011·The Journal of Infectious Diseases·Duangdao NantakomolKesinee Chotivanich
Nov 24, 2011·International Journal of Biological Sciences·Douglas J PerkinsJohn Michael Ong'echa
Sep 5, 2012·Immunologic Research·Anatoly V RubtsovPhilippa Marrack
May 18, 2013·Nature Reviews. Immunology·Luke A J O'NeillAndrew G Bowie
Aug 8, 2013·Proceedings of the National Academy of Sciences of the United States of America·Kira RubtsovaPhilippa Marrack
Oct 23, 2013·The Journal of Experimental Medicine·Natalia V GiltiayKeith B Elkon
Oct 18, 2014·Nature Reviews. Immunology·Ricardo T GazzinelliDouglas T Golenbock
Aug 25, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kira RubtsovaPhilippa Marrack
Dec 20, 2015·Immunological Reviews·Martin S NaradikianMichael P Cancro
Feb 13, 2016·Cell Host & Microbe·Cristina Fernandez-AriasAna Rodriguez
Apr 14, 2016·The Journal of Experimental Medicine·Phillip P DomeierZiaur S M Rahman
Apr 14, 2016·The Journal of Experimental Medicine·Shaun W JacksonDavid J Rawlings
Jul 20, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Burton E BarnettE John Wherry
Dec 13, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jenna J GuthmillerNoah S Butler

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Citations

Nov 6, 2018·ELife·Damián Pérez-MazliahJean Langhorne
Apr 3, 2019·JCI Insight·Christopher SundlingAnna Färnert
Nov 26, 2019·European Journal of Immunology·Hideki Ueno
Jul 21, 2020·PLoS Neglected Tropical Diseases·Juan Rivera-CorreaAna Rodriguez
Apr 20, 2019·Frontiers in Immunology·Ann Ly, Diana S Hansen
Jul 1, 2020·Frontiers in Cellular and Infection Microbiology·Luiza Carvalho MourãoÉrika Martins Braga
Apr 4, 2019·Nature Reviews. Immunology·Samarchith P KurupJohn T Harty
Nov 17, 2019·Immunological Reviews·Damián Pérez-MazliahJean Langhorne
Jun 20, 2020·JCI Insight·Iset Medina VeraKami Kim
Oct 2, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maria PopescuGary M Winslow
Jan 20, 2021·Journal of Leukocyte Biology·Debopam Ghosh, Jason S Stumhofer
Dec 29, 2020·Frontiers in Cellular and Infection Microbiology·Chunmei CaiXiao Yu
Dec 12, 2020·Brain Communications·Malou JanssenMarvin M van Luijn
May 5, 2018·Trends in Immunology·Juan Rivera-Correa, Ana Rodriguez
Apr 9, 2021·The Journal of Experimental Medicine·Rahul VijayNoah S Butler
Jan 4, 2022·Scandinavian Journal of Immunology·Aaron FlemingMenna R Clatworthy
Feb 4, 2022·PLoS Pathogens·Ali Hassan, Nicolas Blanchard

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Methods Mentioned

BETA
ELISA
transgenic
flow cytometry
FACS

Software Mentioned

GraphPad
FCAP Array
GraphPad Prism

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