Avian T helper one/two immune response balance can be shifted toward inflammation by antigen delivery to scavenger receptors

Department of Biological Sciences, University of Arkansas, Fayetteville 72701, USA.

Whether immune responses are dominated by inflammation or antibody production is often key to surviving infections. Therefore, differential control of these immune pathways determined by CD4 T cells is of fundamental interest for vaccine design. Little is known about how inflammatory [T helper cell (Th) type 1 (Th1)] versus antibody-inducing (Th2) choices are controlled in domestic fowl. To address this, MHC-matched chickens were immunized to test whether antibody-dominated Th2 or inflammatory Th1 responses could be preferentially activated, and our findings subsequently extended to outbred broiler breeders. Strategies used were known to shift the response in mice from Th2 to Th1 by delivering the injected antigen preferentially to macrophages. The model antigen, BSA, was maleylated to allow binding to scavenger receptors (SR) present on mammalian macrophages. Maleyl-BSA bound well in receptor-specific fashion to a chicken macrophage cell line. Compared with native BSA, immunization with SR-binding, maleyl-BSA modulated the immune response toward the Th1 pathway, as evident by increases in the magnitude of in vivo inflammatory reactions and declines in antibody-making responses. Initiation of a maleyl-BSA Th1 pathway is further supported by the enhanced ability of splenocytes to express mRNA for interferon-gamma in response to antigens. Together, these data establish the presence and functional relevance of SR in domestic fowl as well as provide a system for investigating the mechanisms controlling Th1/Th2 pathways in chickens. Moreover, the ability to direct immune responses toward either pathway by antigen maleylation will contribute significantly to the development of better vaccines for poultry diseases.

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