IL-24 protects againstSalmonella typhimuriuminfection by stimulating early neutrophil Th1 cytokine production, which in turn activates CD8+T cells

Salmonella are important intracellular pathogens in humans and other animal hosts. IL-24 is a novel tumour suppressor and can mediate induction of Th1-type cytokines from PBMC. However, the immunological consequences of this cytokine during intracellular pathogen infection in vivo remain unclear. In the present study, we used a virulent S. typhimurium C5 infected mouse model of typhoid fever to demonstrate that administration of exogenous IL-24 had a protective effect against the bacteria. The IL-24 glycosylation site mutant, in contrast, showed a decreased protective effect. Furthermore, the protective effect of IL-24 was abrogated in IFN-gamma KO mice. More importantly, we demonstrated that IL-24 predominately stimulated neutrophils to produce IFN-gamma and IL-12, subsequently activating CD8+ T cells both in vivo and in vitro. In addition, IL-24 could induce neutrophils to produce NO. These data indicate that the neutrophils activated by IL-24 may play important roles in host defence against Salmonella infection in vivo. Our findings support the development of a novel cytokine immunotherapy against Salmonella.