Exploring the mechanisms that lead to delayed CD8+ T cell response against Salmonella Typhimurium

Abstract

Salmonella Typhimurium (ST) infection of murine hosts results in a critical delay in CD8+ T cell expansion, and survival is therefore solely dependent on the alternate, innate immune system. A compromised innate immune system is therefore catastrophic for the host. The mechanism of delayed CD8+ T cell response was therefore explored. Results indicate that the delay in CD8+ T cell activation is related to the inefficient interaction of antigen-presenting cells with ST: ST is not readily taken up by antigen-presenting cells, a significant fraction of ST escapes into the extracellular niches to avoid detection, and within the infected cell ST resides within phagosomes which does not lead to antigen-processing through the direct antigen-processing pathway. All these mechanisms lead to activation of CD8+ T cells by the alternate, cross-presentation pathway, which does not operate efficiently in all the strains of mice.