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

William G. C. Horsnell*, Matthew G. Darby, Jennifer C. Hoving, Natalie Nieuwenhuizen, Henry J. McSorley, Hlumani Ndlovu, Saeeda Bobat, Matti Kimberg, Frank Kirstein, Anthony J. Cutler, Benjamin DeWals, Adam F. Cunningham, Frank Brombacher

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Article number1003662
Number of pages12
JournalPLoS Pathogens
Volume9
Issue number10
DOIs
Publication statusPublished - Oct 2013

Keywords / Materials (for Non-textual outputs)

  • ALTERNATIVELY ACTIVATED MACROPHAGES
  • T-CELLS
  • NEMATODE PARASITES
  • HELMINTH INFECTION
  • PROTECTIVE IMMUNITY
  • TYPE-2 IMMUNITY
  • CUTTING EDGE
  • RESPONSES
  • MEMORY
  • SALMONELLA

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