Limited interleukin-18 response in Salmonella-infected murine macrophages and in Salmonella-infected mice.
Optimal immune responses against an intracellular bacterial pathogen, such as Salmonella, involve the production of gamma interferon (IFN-gamma), which activates macrophages. It has recently been suggested that, interleukin-18 (IL-18), in addition to IL-12, contributes to the induction of IFN-gamma following infection. Given this hypothesis, an optimal host immune response against intracellular bacterial pathogens would include the induction of IL-18 secretion by macrophages due to Salmonella infection. We questioned whether Salmonella could induce macrophages to upregulate their expression of IL-18 mRNA and secretion of IL-18. With cultures of murine macrophages, we were surprised to find that infection by wild-type Salmonella dublin resulted in decreased expression of IL-18 mRNA and IL-18 secretion rather than an increase. Reduction of macrophage-derived IL-18 expression by wild-type Salmonella occurred early in the response, suggesting a direct effect. Furthermore, mice orally inoculated with wild-type Salmonella were shown to have reduced IL-18 mRNA expression at mucosal sites within hours postinoculation. Together these studies demonstrate Salmonella-induced reductions in IL-18 expression, suggesting that this intracellular pathogen may be capable of limiting a potentially protective immune response.
Elhofy
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Department of Biology, University of North Carolina-Charlotte, Charlotte, North Carolina 28223, USA.
Bost
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KL
D000595:Amino Acid Sequence; D000818:Animals; D007106:Immune Sera / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D012481:Salmonella Infections, Animal / Q000276:immunology*
D007106:Immune Sera; D020382:Interleukin-18; D012333:RNA, Messenger; D007371:Interferon-gamma