IL-4Rα-Associated Antigen Processing by B Cells Promotes Immunity in Nippostrongylus brasiliensis Infection

被引:28
作者
Horsnell, William G. C. [1 ,2 ]
Darby, Matthew G. [1 ,2 ]
Hoving, Jennifer C. [1 ,2 ]
Nieuwenhuizen, Natalie [1 ,2 ]
McSorley, Henry J. [3 ]
Ndlovu, Hlumani [1 ,2 ]
Bobat, Saeeda [4 ,5 ]
Kimberg, Matti [1 ,2 ]
Kirstein, Frank [1 ,2 ]
Cutler, Anthony J. [1 ,2 ]
DeWals, Benjamin [1 ,2 ]
Cunningham, Adam F. [4 ,5 ]
Brombacher, Frank [1 ,2 ]
机构
[1] Univ Cape Town, ICGEB, ZA-7925 Cape Town, South Africa
[2] Univ Cape Town, IIDMM, Div Immunol, ZA-7925 Cape Town, South Africa
[3] Univ Edinburgh, Ashworth Labs, Inst Immunol & Infect Res, Edinburgh, Midlothian, Scotland
[4] Univ Birmingham, Sch Immun & Infect, Birmingham, W Midlands, England
[5] Univ Birmingham, MRC, Ctr Immune Regulat, Birmingham, W Midlands, England
基金
英国医学研究理事会; 新加坡国家研究基金会;
关键词
T-CELLS; HELMINTH INFECTIONS; PROTECTIVE IMMUNITY; TYPE-2; IMMUNITY; CUTTING EDGE; RESPONSES; ACTIVATION; MEMORY; IL-4; EXPRESSION;
D O I
10.1371/journal.ppat.1003662
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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-4R alpha and IL-13; but not IL-4. Protection did not associate with parasite specific antibody responses. Re-infection of B cell-specific IL-4R alpha(-/-) 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-4R alpha expressing B cells into naive BALB/c mice, but not IL-4R alpha 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-4R alpha-responsive B cells producing IL-13 contribute significantly to CD4(+) T cell-mediated protective immunity against N. brasiliensis infection.
引用
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页数:12
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