PLASMABLASTS CONSTITUTE AN EARLY CONTROL OF TRYPANOSOMA CRUZI REPLICATION AND MAY REGULATE INFLAMMATION AND IMMUNOPATHOLOGY DURING THE INFECTION

GOROSITO-SERRÁN, MELISA; FIOCCA VERNENGO, FACUNDO; BECCARIA, CRISTIAN GABRIEL; JEAN CAPPELLO ; YEPING CAI; IAN COCKBURN; MAYURA WAGLE ; IAN PARISH; PRAE PONGTORNPIPAT ; ELINA ZUÑIGA ; MONTES, CAROLINA L.; ACOSTA RODRIGUEZ E V; GARCIA DE VINUESA, CAROLA; GRUPPI, ADRIANA

BUENOS AIRES

Congreso; Reunión Conjunta de Sociedades de Biociencias 2017; 2017

SAI - SAIC - SAP - SAIB etc

1706) PLASMABLASTS CONSTITUTE AN EARLY CONTROLOF TRYPANOSOMA CRUZI REPLICATION ANDMAY REGULATE INFLAMMATION AND IMMUNOPATHOLOGYDURING THE INFECTIONMelisa Gorosito Serran (1), Facundo Fiocca Vernengo (1),Cristian Gabriel Beccaria (1), Jean Cappello (2), Yeping Cai(2), Ian Cockburn (2), Mayura Wagle (2), Ian Parish (2), PraePongtornpipat (3), Elina Zuñiga (3), Carolina Lucia Montes(1), Eva Virginia Acosta Rodriguez (1), Carola Garcia De Vinuesa(2), Adriana Gruppi (1)(1) CIBICI. (2) John Curtin School Of Medical Research ?ANU. (3) University Of California San Diego.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<0.0001)but despite PB-absence these mice controlled parasitemia, showinga reduction of trypomastigotes in blood at day 12pi. Infected PB-deficientmice also presented a significant increase in PD1+CD4+Tcells, particularly those IFNg+TNF+ at day 18pi (p<0.001), indicatingthat CD4+T cells were disregulated in absence of PB. Furthermore,livers of infected PB-deficient mice presented more lesions relatedto inflammation. In vitro, co-culture of cell-sorted PD-L1+PB withCD4+ and CD8+T cells showed that PB suppressed cytokine productionby T cells in a PD-1/PD-L1 mechanism.In conclusion, PB are key players during T. cruzi infection becausethey constitute an early control of parasite replication and may regulateinflammation and immunopathology.Keywords: Trypanosoma cruzi, Plasmablasts, PD-1/PD-L1, Inflammation,B cells.