PD-L1hi plasmablasts limit the T cell response during the acute phase of parasite infections

Author:

Serrán Melisa Gorosito,Vernengo Facundo Fiocca,Almada Laura,Beccaria Cristian G,Canete Pablo F,Alegre Jonathan Rocco,Boari Jimena Tosello,Ramello Maria Cecilia,Wehrens Ellen,Cai Yeping,Zuniga I Elina,Montes Carolina L,Rodriguez Eva V Acosta,Cockburn Ian A.,Vinuesa Carola G,Gruppi Adriana

Abstract

ABSTRACTDuring infections with protozoan parasites or virus, T cell immunosuppression is generated simultaneously with a high B cell activation. Here, we show that in T. cruzi infection, all plasmablasts detected had higher surface expression of PD-L1, than other mononuclear cells. PD-L1hi plasmablasts were induced in vivo in an antigen-specific manner and required help from Bcl-6+CD4+T cells. PD-L1hi expression was not a characteristic of all antibody-secreting cells since plasma cells found during the chronic phase of infection express PD-L1 but at lower levels. PD-L1hi plasmablasts were also present in mice infected with Plasmodium or with lymphocytic choriomeningitis virus, but not in mice with autoimmune disorders or immunized with T cell-dependent antigens. PD-L1hi plasmablasts suppressed T cell response, via PD-L1, in vitro and in vivo. Thus, this study reveals that extrafollicular PD-L1hi plasmablasts, which precede the germinal center (CG) response, are a suppressive population in infections that may influence T cell response.Brief summaryPathogens develop different strategies to settle in the host. We identified a plasmablats population induced by pathogens in acute infections which suppress T cell response.

Publisher

Cold Spring Harbor Laboratory

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