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

Whether immune responses are dominated by inflammation or antibody producti on 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 tes t whether antibody-dominated Th2 or inflammatory Th1 responses could be pre ferentially activated, and our findings subsequently extended to outbred br oiler breeders. Strategies used were known to shift the response in mice fr om Th2 to Th1 by delivering the injected antigen preferentially to macropha ges. The model antigen, BSA, was maleylated to allow binding to scavenger r eceptors (SR) present on mammalian macrophages. Maleyl-BSA bound well in re ceptor-specific fashion to a chicken macrophage cell line. Compared with na tive BSA, immunization with SR-binding, maleyl-BSA modulated the immune res ponse toward the Th1 pathway, as evident by increases in the magnitude of i n vivo inflammatory reactions and declines in antibody-making responses. In itiation of a maleyl-BSA Th1 pathway is further supported by the enhanced a bility of splenocytes to express mRNA for interferon-gamma in response to a ntigens. Together, these data establish the presence and functional relevan ce of SR in domestic fowl as well as provide a system for investigating the mechanisms controlling Th1/ Th2 pathways in chickens. Moreover, the abilit y to direct immune responses toward either pathway by antigen maleylation w ill contribute significantly to the development of better vaccines for poul try diseases.