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PLoS Pathog ; 9(10): e1003662, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24204255

ABSTRACT

In this study, B cell function in protective T(H)2 immunity against N. brasiliensis infection was investigated. Protection against secondary infection depended on IL-4Rα and IL-13; but not IL-4. Protection did not associate with parasite specific antibody responses. Re-infection of B cell-specific IL-4Rα⁻/⁻ mice resulted in increased worm burdens compared to control mice, despite their equivalent capacity to control primary infection. Impaired protection correlated with reduced lymphocyte IL-13 production and B cell MHC class II and CD86 surface expression. Adoptive transfer of in vivo N. brasiliensis primed IL-4Rα expressing B cells into naïve BALB/c mice, but not IL-4Rα or IL-13 deficient B cells, conferred protection against primary N. brasiliensis infection. This protection required MHC class II compatibility on B cells suggesting cognate interactions by B cells with CD4⁺ T cells were important to co-ordinate immunity. Furthermore, the rapid nature of these protective effects by B cells suggested non-BCR mediated mechanisms, such as via Toll Like Receptors, was involved, and this was supported by transfer experiments using antigen pulsed Myd88⁻/⁻ B cells. These data suggest TLR dependent antigen processing by IL-4Rα-responsive B cells producing IL-13 contribute significantly to CD4⁺ T cell-mediated protective immunity against N. brasiliensis infection.


Subject(s)
Antigen Presentation , B-Lymphocytes/immunology , Immunity, Cellular , Nippostrongylus/immunology , Receptors, Cell Surface/immunology , Strongylida Infections/immunology , Th2 Cells/immunology , Animals , B-Lymphocytes/pathology , B7-2 Antigen/genetics , B7-2 Antigen/immunology , Histocompatibility Antigens Class II/genetics , Histocompatibility Antigens Class II/immunology , Interleukin-13/genetics , Interleukin-13/immunology , Mice, Inbred BALB C , Mice, Knockout , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/immunology , Receptors, Cell Surface/genetics , Strongylida Infections/genetics , Strongylida Infections/pathology , Th2 Cells/pathology , Toll-Like Receptors/genetics , Toll-Like Receptors/immunology
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