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

Abstract

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.

• Authors: Sasha Silva-Barrios, Mélina Smans, Claudia U Duerr, Salman T Qureshi, Jörg H Fritz, Albert Descoteaux, Simona Stäger
• Journal: Cell reports (Cell Rep) Vol. 15 Issue 11 Pg. 2427-37 (06 14 2016) ISSN: 2211-1247 [Electronic] United States
• PMID: 27264176 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Interferon Type I
• Membrane Transport Proteins
• RNA, Messenger
• Toll-Like Receptors
• UNC93B1 protein, mouse
• Interleukin-10
• Receptor, Interferon alpha-beta

Topics

• Animals
• B-Lymphocytes (immunology, parasitology)
• Disease Progression
• Endosomes (metabolism)
• Hypergammaglobulinemia (complications, immunology)
• Immunity, Innate
• Interferon Type I (genetics, metabolism)
• Interleukin-10 (genetics, metabolism)
• Leishmania donovani (physiology)
• Leishmaniasis (genetics, immunology, parasitology, pathology)
• Lymphocyte Activation (immunology)
• Membrane Transport Proteins (deficiency, metabolism)
• Mice, Inbred C57BL
• RNA, Messenger (genetics, metabolism)
• Receptor, Interferon alpha-beta (metabolism)
• Spleen (pathology)
• Th1 Cells (immunology)
• Toll-Like Receptors (metabolism)
• Up-Regulation (genetics)