Evidence for the requirement for CD40—CD154 interactions in resistance to infections with attenuated Salmonella

Abstract

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-gamma 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.

Membrane Vesicles Are Immunogenic Facsimiles of Salmonella typhimurium That Potently Activate Dendritic Cells, Prime B and T Cell Responses, and Stimulate Protective Immunity In Vivo

“…For protection experiments, reduction in bacterial replication was used as a measure of protective immunity, and MV-immune mice were infected via the i.p. route with ϳ1 ϫ 10 5 CFU SL3261, which allows the survival of infected animals (55)(56)(57)(58)(59)(60)(61). After MV immunization and live bacterial challenge (see above), bacterial burden in infected tissues was used as a measure of protective immunity.…”

“…6), indicating that MV-induced B and T cells respond to infection with live bacteria. Because it is firmly established that protectively immunized mice inhibit bacterial replication during live Salmonella challenge (41), we determined organ CFU as a measure of protective immunity in MV-immune mice infected with viable Salmonella SL3261, which allows the survival of infected animals (55)(56)(57)(58)(59)(60)(61). In contrast to sham-immunized controls, MV-immune mice had decreased bacterial CFU in all organs measured after infection with live Salmonella (Fig.…”

Cholinergic stimulation of the immune system protects against lethal infection by Salmonella enterica serovar Typhimurium

“…Protection against S. typhimurium requires Th1-type immune responses. [22][23][24]43 Moreover, a robust antibody response is known to be required for resistance against virulent Salmonella infection. 22,44,45 Our results demonstrated that, contrary to expectations, paraoxon treatment rendered the animals more resistant to Salmonella infections.…”

“…To determine if paraoxon exposure had any effect on susceptibility to infection, mice were treated with paraoxon for 3 weeks and then inoculated with a lethal dose of the facultative enteric pathogen S. typhimurium . Protection against S. typhimurium requires Th1‐type immune responses 22–24,43 . Moreover, a robust antibody response is known to be required for resistance against virulent Salmonella infection 22,44,45 .…”