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Infection and Immunity, December 1998, p. 5862-5866, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Salmonella typhimurium Infection in Mice Induces Nitric Oxide-Mediated Immunosuppression through a Natural Killer Cell-Dependent Pathway

Martin G. Schwacha,dagger Joseph J. Meissler Jr., and Toby K. Eisenstein*

Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140

Received 20 July 1998/Returned for modification 1 September 1998/Accepted 21 September 1998

Splenocytes isolated from C57BL/6J female mice 3 to 7 days after inoculation with an attenuated strain of Salmonella typhimurium produced high levels of nitric oxide (39 to 77 µM) and gamma interferon (IFN-gamma ). Additionally, spleen cell cultures from Salmonella-inoculated mice were markedly suppressed in their ability to generate an in vitro plaque-forming cell (PFC) response to sheep erythrocytes. Depletion of natural killer (NK) cells from the immune splenocyte population markedly reduced nitric oxide production, prevented suppression of PFC responses, and completely abrogated IFN-gamma release. Treatment of NK cell-depleted immune cells with IFN-gamma restored nitric oxide production to levels comparable to those of intact immune cells and also restored the immunosuppression. These results suggest that NK cells regulate the induction of nitric oxide-mediated immunosuppression following infection with S. typhimurium through the production of IFN-gamma .

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Temple University School of Medicine, 3400 North Broad St., Philadelphia, PA 19140. Phone: (215) 707-3585. Fax: (215) 707-7920. E-mail: tke{at}astro.ocis.temple.edu.

dagger Present address: Center for Surgical Research, Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence, RI 02903.

Infection and Immunity, December 1998, p. 5862-5866, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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