Innate Immune B Cell Activation by Leishmania donovani Exacerbates Disease and Mediates Hypergammaglobulinemia.

Abstract

Participation of B cells in the immune response byvarious antibody-independent mechanisms has recently been uncovered. B cells producing cytokines have been described for several infections and appear to regulate the adaptive immune response. B cell activation by Leishmania donovani results in disease exacerbation. How Leishmania activates B cells is still unknown. We show that L.donovani amastigotes activate B cells by triggering endosomal TLRs; this activation leads to the induction of various cytokines. Cytokine expression is completely abrogated in B cells from Ifnar(-/-) mice upon exposure to L.donovani, suggesting an involvement of IFN-I in a positive feedback loop. IFN-I also appears to enhance the expression of endosomal TLRs following exposure to L.donovani. Cell-specific ablation of endosomal TLR signaling in B cells revealed that innate B cell activation by L.donovani is responsible for disease exacerbation through IL-10 and IFN-I production and for the promotion of hypergammaglobulinemia.