Basic leucine zipper transcription factor, ATF-like (BATF) is essential for the development of protective immunity against parasitic helminth infection (MPF1P.779)

Abstract

Abstract Parasitic helminth infections afflict roughly a quarter of the world’s population. Immunity against parasitic helminth infection relies on the induction of allergic inflammation. Major hallmarks of allergic inflammation, such as IgE, eosinophilia, and mucus production, depend on the cytokines interleukin-4 (IL-4) and IL-13. In mice, IL-4 from CD4+ follicular T helper (Tfh) cells is required for IgE production, while IL-13 from CD4+ T-helper 2 (Th2) cells is required for worm clearance and mucus production. The basic leucine zipper transcription factor, ATF-like (BATF) is critical for Tfh function, however its necessity in Th2 cell development and IL-4 production remains unclear. To investigate the role of BATF in the context of allergic inflammation, we infected wild-type and BATF-deficient mice with the helminth Nippostrongylus brasiliensis to compare the resultant immune responses. In wild-type mice, N. brasiliensis infection induced a robust response as indicated by lung eosinophilia, high serum IgE, and worm expulsion. In contrast, BATF-deficient mice exhibited dramatically reduced eosinophilia, no IgE, and were unable to clear parasites from the intestine. Studies with IL-4-reporter mice revealed that these defects in allergic immunity were attributed to impaired Tfh and Th2 cell development. These findings suggest that BATF plays a central role in protection against helminths, and BATF is critical for the development of both Th2 and Tfh cells during allergic responses.