Parasite Immunity Orchestrated by Th2 Cells

University Of California, San Francisco, San Francisco CA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Parasitic helminths elicit host immune responses characterized by infiltration of tissues with Th2 cells and eosinophils, and the generation of high IgE in serum. These responses reflect stereotyped host mucosal and systemic immunity orchestrated by Th2 cells. Through elaboration of IL-4 and IL-13, Th2 cells organize a focused response necessary to mediate the physiologic alterations of the epithelial barrier, including enhanced mucus secretion and epithelial cell turnover. Despite these observations, the precise cells which elaborate the IL-4 and IL-13 required to mediate immunity are unknown, and how these cells might contribute to the pathology associated with chronic infestations is poorly understood. We have genetically marked cells that produce IL-4 in the mouse, thus allowing us to follow the cells that contribute this functionally important cytokine. Using infection with Nippostrongylus brasiliensis as well as other challenges, we find only 3 cell types recruited to tissues undergoing a type 2 immune response in a highly stereotyped manner. We have generated a series of mouse lines with lineage-specific markers in innate and adaptive cells that will enable a systemic evaluation of the cytokine contributions by each cell implicated in this response. We have established systems to follow these cells over time throughout the tissues of the mouse. These novel reagents utilize a functional tracking system to allow a critical evaluation of the key cells and their interactions as required to carry out and sustain type 2 immunity. These findings will contribute significantly to our understanding of this poorly understood but universal immune response, which is shared by human responses to widely endemic parasitic worms, but also by allergic reactions underlying atopy and asthma. [unreadable] [unreadable] [unreadable]