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

J Rivera-Correa; J J Guthmiller; R Vijay; C Fernandez-Arias; M A Pardo-Ruge; S Gonzalez; N S Butler; A Rodriguez

doi:10.1038/s41467-017-01476-6

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

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

J Rivera-Correa, J J Guthmiller, R Vijay, C Fernandez-Arias, M A Pardo-Ruge, S Gonzalez, N S Butler and A Rodriguez

Nature communications, Vol.8(1), 1282

11/03/2017

DOI: 10.1038/s41467-017-01476-6

PMCID: PMC5670202

PMID: 29101363

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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. Supplementary material and peer review file available at 10.1038/s41467-017-01476-6.

Details

Title: Subtitle: Plasmodium DNA-mediated TLR9 activation of T-bet + B cells contributes to autoimmune anaemia during malaria
Creators: J Rivera-Correa - Department of Microbiology, New York University School of Medicine, New York, NY, 10010, USA
J J Guthmiller - Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA
R Vijay - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, 52242, USA
C Fernandez-Arias - Department of Microbiology, New York University School of Medicine, New York, NY, 10010, USA
M A Pardo-Ruge - Department of Microbiology, New York University School of Medicine, New York, NY, 10010, USA
S Gonzalez - Department of Microbiology, New York University School of Medicine, New York, NY, 10010, USA
N S Butler - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, 52242, USA
A Rodriguez - Department of Microbiology, New York University School of Medicine, New York, NY, 10010, USA. Ana.Rodriguez@nyumc.org
Resource Type: Journal article
Publication Details: Nature communications, Vol.8(1), 1282
DOI: 10.1038/s41467-017-01476-6
PMID: 29101363
PMCID: PMC5670202
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Publisher: England
Grant note: R01 AI127481 / NIAID NIH HHS T32 AI007180 / NIAID NIH HHS KL2 TR001446 / NCATS NIH HHS UL1 TR001445 / NCATS NIH HHS T32 AI100853 / NIAID NIH HHS TL1 TR001447 / NCATS NIH HHS R01 AI125446 / NIAID NIH HHS
Language: English
Date published: 11/03/2017
Academic Unit: Microbiology and Immunology
Record Identifier: 9984001134502771

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