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Microbiology Society logo Microbiology

Volume 155, Issue 8

Novel role of the nitrite transporter NirC in pathogenesis: SPI2-dependent suppression of inducible nitric oxide synthase in activated macrophages Free

Abstract

Activation of macrophages by interferon gamma (IFN-) and the subsequent production of nitric oxide (NO) are critical for the host defence against serovar Typhimurium infection. We report here the inhibition of IFN--induced NO production in RAW264.7 macrophages infected with wild-type . This phenomenon was shown to be dependent on the gene, which encodes a potential nitrite transporter. We observed a higher NO output from IFN--treated macrophages infected with a mutant of . The mutant also showed significantly decreased intracellular proliferation in a NO-dependent manner in activated RAW264.7 macrophages and in liver, spleen and secondary lymph nodes of mice, which was restored by complementing the gene . Under acidified nitrite stress, a twofold more pronounced NO-mediated repression of SPI2 was observed in the knockout strain compared to the wild-type. This enhanced SPI2 repression in the knockout led to a higher level of STAT-1 phosphorylation and inducible nitric oxide synthase (iNOS) expression than seen with the wild-type strain. In iNOS knockout mice, the organ load of the knockout strain was similar to that of the wild-type strain, indicating that the mutant is exclusively sensitive to the host nitrosative stress. Taken together, these results reveal that intracellular evade killing in activated macrophages by downregulating IFN--induced NO production, and they highlight the critical role of as a virulence gene.

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  • Published Online:
Keyword(s): BMDM, bone-marrow-derived macrophages , FBS, fetal bovine serum , IFN-γ, interferon gamma , iNOS, inducible nitric oxide synthase , JAK-STAT, Janus kinase/signal transducer and activator of transcription , L-NIL, l-N6-iminoethyllysine , MLN, mesenteric lymph nodes , NED, N-(naphthyl)ethylenediamine dihydrochloride , RNS, reactive nitrogen species , ROI, reactive oxygen intermediates , SOCS-3, suppressor of cytokine signalling-3 and SPI2, Salmonella pathogenicity island 2
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2009-08-01
2025-04-25
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Novel role of the nitrite transporter NirC in Salmonella pathogenesis: SPI2-dependent suppression of inducible nitric oxide synthase in activated macrophages
Microbiology 155, 2476 (2009); https://doi.org/10.1099/mic.0.029611-0
/content/journal/micro/10.1099/mic.0.029611-0
/content/journal/micro/10.1099/mic.0.029611-0
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