Early responses to Salmonella typhimurium infection in mice occur at focal lesions in infected organs.

Salmonella typhimurium causes an invasive disease in mice that has similarities to human typhoid, with key roles for cytokines and possibly also inducible nitric oxide synthase (iNOS), in mediating host responses to infection. In this paper we demonstrate that iNOS mRNA, protein and enzyme activity is induced within spleens and livers of infected mice as early as 5 h post-infection. Immunohistochemistry and in situ hybridization indicated that iNOS expression occurs predominantly in macrophages in localized, discrete foci in the infected organs. iNOS activity in spleen and liver was not detectable in uninfected control mice. The presence of mRNA encoding pro-inflammatory cytokines (TNFalpha, IL-1beta and IFNgamma) in infected organs was measured using RT-PCR, all three being present from 2 h post-infection onwards, but not before. These data show that there is a very early host response to S. typhimurium infection in mice, limited to foci within the infected organs.