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Plasmodium DNA-mediated TLR9 activation of T-bet(+) B cells contributes to
autoimmune anaemia during malaria
#MMPMID29101363
Rivera-Correa J
; Guthmiller JJ
; Vijay R
; Fernandez-Arias C
; Pardo-Ruge MA
; Gonzalez S
; Butler NS
; Rodriguez A
Nat Commun
2017[Nov]; 8
(1
): 1282
PMID29101363
show ga
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-? receptor
(IFN-?R) 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-?R activation of T-bet(+) B cells is a mechanism underlying
infection-induced autoimmune-like responses.
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