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Nitric Oxide Produced by Murine Dendritic Cells is Cytotoxic for Intracellular Salmonella enterica sv. Typhimurium
Author(s) -
Eriksson S.,
Chambers B. J.,
Rhen M.
Publication year - 2003
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.2003.01330.x
Subject(s) - salmonella enterica , intracellular , microbiology and biotechnology , salmonella , nitric oxide , macrophage , biology , intracellular parasite , nitric oxide synthase , innate immune system , cytotoxic t cell , lipopolysaccharide , bacteria , immune system , immunology , biochemistry , in vitro , genetics , endocrinology
The pathogenicity of Salmonella enterica serovar Typhimurium has traditionally been correlated with its ability to survive and grow in macrophages. Macrophage‐derived production of nitric oxide (NO) has been implicated as a major innate defence, restricting bacterial proliferation both in macrophage cultures and in mice. In the present study, we show that the ability of primary murine dendritic cells (DCs) to ingest Salmonella is low, but greatly enhanced by serum complement. Ingestion of bacteria was followed by the expression of inducible nitric oxide synthase (iNOS), as well as by NO production. iNOS mRNA was detected as early as 6 h post infection and production of NO 12 h post infection, rising further at 16 h post infection . Inhibition of the iNOS activity with the inhibitor N ‐monomethyl‐ l ‐arginine or using DCs from iNOS –/– mice resulted in increased intracellular bacterial yields. To further define the potential defensive role of DC‐derived NO, the actual intracellular replication rate of S . Typhimurium in DCs was measured. DC‐derived NO was shown to exert a bactericidal effect, whereas the effect of NO in macrophage‐like J774‐A.1 cells was found to be bacteriostatic. These results identified an important role for NO in restricting S . Typhimurium survival in DCs, indicating that DCs may actively participate in the innate defence against intracellular pathogens.