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

Abstract

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 (D10 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 D10 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 cell 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.

Bacterial Pathogens Induce Abscess Formation by CD4+T-Cell Activation via the CD28–B7-2 Costimulatory Pathway

“…This work has shown that CD28-B7 interactions have a prominent role in governing the host immune response to parasitic and bacterial infections (10,24,27,40,41,43). The goal of the present work was to determine the specific role of T cells in intra-abdominal abscess formation.…”

Antibody Is Required for Protection against Virulent but Not AttenuatedSalmonella entericaSerovar Typhimurium

“…Macrophages have been shown to upregulate B7 molecules when exposed to Salmonella extracts in vitro (8), indicating that the activation of T-cell responses requiring CD28 costimulation may be enhanced by bacterial products. Indeed, lipopolysaccharide (LPS) is often used as an adjuvant for protein antigens due to its capacity to induce costimulatory molecules and the production of inflammatory cytokines by antigen-presenting cells (16,34,36).…”

Priming of T‐Cell Responses in Mice by Porins of Salmonella typhimurium

“…Elution was performed by using a linear salt gradient (20 ml): 20 mM Tris (pH 7.5) to 20 mM Tris containing 1 M NaCl (pH 7.5). Fractions were dialysed and analysed on SDS-PAGE [5].…”

“…In addition, an important co-stimulatory signal must be delivered from the antigen-presenting cell. In earlier studies, we reported that infection with live S. typhimurium in vitro causes a decreased expression of B7 and intracellular adhesion molecule-1 (ICAM-1) and that these changes contribute to the depressed CMI responses during Salmonella infection [5].…”