IL-24 protects against Salmonella typhimurium infection 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.
Ma
Yunfeng
Y
State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immune-related Diseases and Oversea Open Laboratory, Wuhan University School of Medicine, Wuhan, P. R. China.
Chen
Haidan
H
Wang
Qilong
Q
Luo
Fengling
F
Yan
Jun
J
Zhang
Xiao-Lian
XL
D000818:Animals; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D012481:Salmonella Infections, Animal / Q000378:metabolism* / Q000382:microbiology / Q000517:prevention & control; D012486:Salmonella typhimurium / Q000187:drug effects / Q000254:growth & development; D018417:Th1 Cells / Q000378:metabolism; D014162:Transfection; D014435:Typhoid Fever / Q000276:immunology / Q000378:metabolism; D000099180:Interleukin-24
D016207:Cytokines; D007371:Interferon-gamma; D018664:Interleukin-12; D007378:Interleukins; D009569:Nitric Oxide; D011993:Recombinant Fusion Proteins; D000099180:Interleukin-24