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

Sasha Silva-Barrios (1) , Mélina Smans (1) , Claudia U Duerr (2) , Salman T Qureshi (2, 3) , Jörg H Fritz (2) , Albert Descoteaux (1) , Simona Stäger (1)

1 INRS-IAF - Institut Armand Frappier
2 McGill University = Université McGill [Montréal, Canada]
3 MUHC - McGill University Health Center [Montreal]

Participation of B cells in the immune response by various 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.

Domaines: Sciences du Vivant [q-bio]; Immunologie; Maladies infectieuses

Sasha Silva-Barrios, Mélina Smans, Claudia U Duerr, Salman T Qureshi, Jörg H Fritz, et al.. Innate Immune B Cell Activation by Leishmania donovani Exacerbates Disease and Mediates Hypergammaglobulinemia.. Cell Reports, 2016, 15 (11), pp.2427-37. ⟨10.1016/j.celrep.2016.05.028⟩. ⟨pasteur-01351549⟩