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Infection and Immunity, October 1999, p. 5021-5026, Vol. 67, No. 10
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Limited Interleukin-18 Response in Salmonella-Infected Murine Macrophages and in Salmonella-Infected Mice

Adam Elhofy and Kenneth L. Bost*

Department of Biology, University of North Carolina---Charlotte, Charlotte, North Carolina 28223

Received 22 March 1999/Returned for modification 17 May 1999/Accepted 21 July 1999

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.

* Corresponding author. Mailing address: Department of Biology, UNC Charlotte, 9201 University City Blvd., Charlotte, NC 28223. E-mail: klbost{at}emailuncc.edu. Phone: (704) 547-2909. Fax: (704) 547-3128.

Infection and Immunity, October 1999, p. 5021-5026, Vol. 67, No. 10
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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