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-L1 hi plasmablasts were induced in vivo in an antigen-specific manner and required help from Bcl-6 + CD4 + T cells. PD-L1 hi 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-L1 hi 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-L1 hi plasmablasts suppressed T cell response, via PD-L1, in vitro and in vivo. Thus, this study reveals that extrafollicular PD-L1 hi 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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RUNNING TITTLEPD-L1 + plasmablasts control T cell response to understand the delicate balance between protective T cell immunity, immune suppression and parasite establishment.Chagas disease presents an acute phase, both in mice and humans, characterized by a state of immunosuppression in which T. cruzi replicates extensively and induces immunomodulatory molecules that delay parasite-specific T cell effector responses 3-6 .It has been reported that during this phase of T. cruzi infection the expression of PD-1, one of the members of the CD28/CTLA4 family with inhibitory capacity, increases on myocardium infiltrating CD4 + and CD8 + T cells 7 . The cross-linking of PD-1 with any of its two ligands, PD-L1 8 or PD-L2 9 , inhibits the activation of T cells and the production of IL-2 and IFN Many studies have shown that other protozoan parasites such as Plasmodium spp. as well as bacteria and viruses also benefit from the PD-1/PD-L1 pathway to suppress and evade the host's adaptive immunity 10,11 . The activation of the PD-1/PD-L1 pathway would enable the establishment of microorganisms and chronicity [12][13][14] . Accordingly, the blocking of PD-1/PD-L1 signals, in combination with therapeutic immunizations or therapies with cytokines, has been proposed as a strategy to improve the efficacy of vaccinations 15 and to revitalize exhausted T cells 16 .During infection with T. cruzi, blocking PD-1 and PD-L1 or deletion of the PD-1 gene results in a reduction in parasitemia and tissue parasitism, but also increased mortality due to an augmented cardiac inflammatory response 7 . These results reveal that the signaling pathway of PD-1/PD-L1 has an important role in the control of inflammation induced by T. cruzi and provide another perspective on the mechanisms of regulation in the pathogenesis ...