Plasmablasts constitute an early control of Trypanosoma cruzi replication and may regulate inflammation and immunopathology during the infection.

GRUPPI A; MONTES CL; PARISH I; CAI Y; FIOCCA VERNENGO F; GARCIA VINUESA C; ZUÑIGA EI; WAGLE M; CAPPELLO J; GOROSITO SERRÁN M; ACOSTA RODRIGUEZ EV; PONGTORNPIPAT P; COCKBURN I; BECCARIA CG

Congreso; Reunión Conjunta de Sociedades de Biociencias.; 2017

B cells are the only cells that differentiate into antibody-secretingcells (plasmablasts, PB; and plasma cells) and they can also shapeand regulate T cell responses through cytokine production. We havefound that PB generated in Trypanosoma cruzi infection have a highsurface expression of the inhibitory molecule PD-L1 and that thesecells were also present in other infections such as LCMV (Clone13) infection and Malaria. Since the PD1/PDL1 pathway is involvedwith disease in these chronic infections, we studied the biology ofPD-L1+PB generation and function. We have found that PD-L1+PBwere not driven by cytokines such as type I IFN, IFNg, IL-6 andTNF or by TLR2 and TLR4, because PD-L1+PB were present in T.cruzi infected mice deficient in all the cytokines and TLR mentioned.In fact, PD-L1+PB were driven by an antigen specific mechanism,since MD4 mice, whose B cells are specific for Hel, did not generatePB after T. cruzi infection. Additionally, PB generation required Tfhcollaboration since infected Bcl6f/fCD4Cre-pos mice presented adecrease in PB compared to Bcl6f/fCD4Cre-neg mice.Blimp1f/fCD23cre-pos mice infected with T. cruzi presented a significantincrease in parasitemia at day 9 post-infection(pi) (p