Salmonella species include facultative intracellular pathogens which reside preferentially within cells of the host's reticulo-endothelial system. Resistance to Salmonella involves a collaboration between cells of the innate and adaptive immune systems, and protective immunity requires cell-mediated and humoral-immune responses. CD40—CD154 interactions are of central importance in the induction of cellular immune responses. In the present study, CD154-deficient (CD154—/—) mice were used to assess the role of CD40—CD154 interactions in immunity to Salmonella infection. Compared to C57BL/6 (CD154+/+) controls, CD154 —/—mice were hypersusceptible to infection by an attenuated strain of Salmonella enterica serovar Typhimurium (S. typhimurium), as evidenced by a significantly decreased survival rate. CD154—/— mice exhibited a defect in the production of IFN-γ and NO in the acute phase of the disease, which resulted in a failure to control bacterial replication. We conclude that intercellular communications via the CD40—CD154 pathway play a critical role in the induction type-1 cytokine responses and protection against primary infections with attenuated Salmonella.
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