Innate Immune B Cell Activation by Leishmania donovani Exacerbates Disease and Mediates Hypergammaglobulinemia.
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.
Institut Armand Frappier and Center for Host-Parasite Interactions, INRS, 531 Boulevard des Prairies, Laval QC H7V 1B7, Canada.
Sasha
S
Silva-Barrios
Institut Armand Frappier and Center for Host-Parasite Interactions, INRS, 531 Boulevard des Prairies, Laval QC H7V 1B7, Canada.
Mélina
M
Smans
Department of Microbiology and Immunology and Department of Physiology, Complex Traits Group, McGill University, Montreal, QC H3G 0B1, Canada.
Claudia U
CU
Duerr
Meakins-Christie Laboratories and Department of Medicine, McGill University Health Centre Research Institute, Montreal, QC H4A 3J1, Canada.
Salman T
ST
Qureshi
Department of Microbiology and Immunology and Department of Physiology, Complex Traits Group, McGill University, Montreal, QC H3G 0B1, Canada.
Jörg H
JH
Fritz
Institut Armand Frappier and Center for Host-Parasite Interactions, INRS, 531 Boulevard des Prairies, Laval QC H7V 1B7, Canada.
Albert
A
Descoteaux
Institut Armand Frappier and Center for Host-Parasite Interactions, INRS, 531 Boulevard des Prairies, Laval QC H7V 1B7, Canada. Electronic address: simona.stager@iaf.inrs.ca.
Simona
S
Stäger
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D018450:Disease Progression; D011992:Endosomes / Q000378:metabolism; D006942:Hypergammaglobulinemia / Q000150:complications / Q000276:immunology*; D007113:Immunity, Innate; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007893:Leishmania donovani / Q000502:physiology*; D007896:Leishmaniasis / Q000235:genetics / Q000276:immunology* / Q000469:parasitology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D026901:Membrane Transport Proteins / Q000172:deficiency / Q000378:metabolism; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000378:metabolism; D013154:Spleen / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D051193:Toll-Like Receptors / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D007370:Interferon Type I; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D051193:Toll-Like Receptors; C512254:UNC93B1 protein, mouse; D016753:Interleukin-10; D053633:Receptor, Interferon alpha-beta