Macrophage-T cell interaction in murine salmonellosis: Selective down-regulation of ICAM-1 and B7 molecules in infected macrophages and its probable role in cell-mediated immunity

Vaccine development and understanding of cellular immune modulatory mechanisms in salmonella infections have been impeded due to the paucity of data on antigens capable of eliciting effective immune responses. The present study was done to evaluate the efficacy of five major purified salmonella antigens (porins, pili, flagella, outer membrane proteins and heat shock proteins) in modulating T cell-macrophage interactions which play a central role in resistance to and recovery from infection with several intracellular pathogens, including salmonella. The results showed that the T cells recovered 10 days post-immunization (D-10 T cells) from mice immunized with porins and outer membrane proteins showed maximum proliferation in the presence of macrophages incubated with dead bacteria; however, this response was decreased when T cells were co-cultured with live Salmonella typhimurium-infected macrophages. Delayed-type hypersensitivity responses, as measured by increased footpad thickness at 24 h, though induced effectively by porins, pili and flagella, were completely abrogated when D-10 T cells were pre-incubated with macrophages infected with live bacteria. The phagocytic and bactericidal ability of normal macrophages, when grown in presence of T cel supernatants, was not influenced by the immunizing agents, but T cell supernatants obtained from mice immunized with porins and heat-shock protein triggered increased bactericidal activity. Further, the expression of the co-stimulatory molecules ICAM-1 and B7 increased with increasing bacteria (dead):macrophage ratio, but this expression was down-regulated upon incubation with live bacteria.