Nitric oxide mediates immunosuppression induced by Listeria monocytogenes infection: Quantitative studies

Amanda Shearer MacFarlane, Duan Huang, Martin G. Schwacha, Joseph J. Meissler, John P. Gaughan, Toby K. Eisenstein

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Our laboratory has shown that immunization of mice with an attenuated strain of Salmonella typhimurium induces profound suppression in the capacity of splenocytes to mount an in vitro antibody plaque-forming cell (PFC) response to sheep red blood cells (SRBC) and to proliferate in response to mitogens. In vitro addition of N(G)-monomethyl-L-arginine (NMMA), an inhibitor of nitric oxide (NO) synthase, to cell cultures from Salmonella-immunized mice completely blocked suppression of the PFC responses, implicating that NO is the suppressor factor. The present study quantified the role of nitric oxide in immunosuppression induced by Listeria monocytogenes, a gram positive intracellular pathogen of macrophages. Listeria infection resulted in suppression of the PFC assay at inoculating doses of greater than 6.5 x 103 colony forming units, with no suppression observed at lower doses. Suppression correlated with increased nitrite production. Addition of NMMA to spleen cell cultures taken from Listeria-infected mice completely blocked suppression of the PFC response, and returned nitrite production to baseline levels. In regard to Listeria-induced suppression of responses to the mitogen, Concanavalin A (Con A), the parameters were different from those observed for the PFC response. There was a direct correlation between the log10 of the inoculating dose of Listeria and degree of immunosuppression, with suppression observed at doses as low as 1 x 103 cells. Addition of NMMA to the Con A-stimulated cultures resulted in reduced nitrite levels, but only partial restoration of the proliferative responses. Co-culture of splenocytes from Listeria inoculated mice with normal splenocytes in media with NMMA and reduced levels of L-arginine resulted in complete reversal of suppressed responses to Con A. Similar differences in ease of reversing suppression of the PFC response, as compared with responses to Con A, were previously noted using cells taken from Salmonella-infected mice. The present results show that a gram positive intracellular pathogen of macrophages, L. monocytogenes, induces immunosuppression in mouse spleen cells by a nitric oxide mediated mechanism that closely parallels that induced by the gram negative pathogen, S. typhimurium.

Original languageEnglish (US)
Pages (from-to)267-277
Number of pages11
JournalMicrobial Pathogenesis
Volume25
Issue number5
DOIs
Publication statusPublished - Nov 1998

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Keywords

  • Immunosuppression
  • Listeria monocytogenes
  • Nitric oxide
  • Spleen cells

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

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