Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 39, Issue 12, Pages 3357-3368Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.200939678
Keywords
CD8(+) T cells; Interleukin-24; Neutrophils; Salmonella typhimurium C5; Th1 cytokines
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Funding
- National Natural Science Foundation of China [30670098, 30870122, 20532020]
- 973 Program [2006CB504300, 2009CB522507]
- Hubei Province Science Technology Department [2006ABD007]
- [2008ZX10003-005]
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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.
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