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

Gorosito Serran, M.; Fiocca Vernengo, F.; Almada, L.; Beccaria, C. G.; Canete, P. F.; Rocco Alegre, J.; Tosello Boari, J.; Ramello, M. C.; Wehrens, E.; Cai, Y.; Zuniga, E. I.; Montes, C. L.; Acosta Rodriguez, E. V.; Cockburn, I. A.; Vinuesa, C. G.; Gruppi, A.

2020-06-12 immunology
10.1101/2020.06.10.142067 bioRxiv
Show abstract

During 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.

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