Interferon‐γ plays a critical role in intestinal immunity against Salmonella typhimurium infection

Abstract

Summary Salmonella bacteria are a major cause of food‐borne infectious diarrhoea and there is great interest in understanding the pathogenesis of Salmonella infection and in vaccine development. Potential vaccines include the aromatic mutants of S. typhimurium. Such non‐lethal Aro mutants have also been useful for studying Salmonella infections in mouse models. Studies of systemic infection, using these Aro mutants, in both normal and cytokine gene knockout mice, indicate that interferon‐γ (IFN‐γ) plays a key role in the resolution of Salmonella infection. The present studies have investigated the outcome of oral infection in mice with attenuated Salmonella because this infection route mimics natural infection in humans. In IFN‐γ gene knockout (IFN‐γ–/–) mice, intestinal immunity was impaired and oral challenge resulted in disseminated septicaemia 2 weeks later. No dissemination of infection was seen in wild‐type mice. In wild‐type mice, both CD4 and CD8 cell numbers increased in the gut following Salmonella challenge, together with increased expression of major histocompatibility complex (MHC) II and vascular cell adhesion molecule‐1 (VCAM‐1). No such changes were seen in IFNγ–/– mice. Following oral challenge, antilipopolysaccharide (LPS) and antiphosphoryl choline antibodies increased by more than 100‐fold in both serum and faecal pellet extracts of IFNγ–/– mice compared with wild‐type mice. Our data show that IFN‐γ production is essential for resolution of enteric Salmonella infection and that antibody has little effect on this process.

Incremental expression of Tlr4 correlates with mouse resistance to Salmonella infection and fine regulation of relevant immune genes

“…Wild-type mice infected with attenuated Salmonella Typhimurium are capable of controlling the infection whereas IFNg-deficient mice succumb to infection owing to unrestricted growth of the bacteria. 21,22 Administration of monoclonal antibodies directed against IL-12 exacerbates the mild disease caused by attenuated Salmonella 23 24 Moreover, the syndrome of Mendelian susceptibility to mycobacterial disease illustrates the importance of IL-12 and IFNg in the host response to Salmonella in humans. 18 Affected patients carrying a pathogenic mutation in one of the genes coding for the IFNg receptor, the IL-12 receptor or the IL-12 p40 subunit show increased susceptibility to environmental mycobacterial species and Salmonella.…”

Immunological and gene expression responses to aSalmonellainfection in the chicken intestine

“…Also in mice the number of CD4 + T-cells increased in the gut following Salmonella challenge [2,15]. Furthermore in the ovary and oviduct of laying hens, increased numbers of CD4 + T-cells were reported after a Salmonella infection [4,25,26].…”

Genetic regulation of host responses to Salmonella infection in mice

“…The growth of attenuated Salmonella Typhimurium aroA À is contained in wild-type mice; however INFg-deficient mice succumb to infection due to unrestricted bacterial proliferation. 33,135 These experiments point out the central role that INFg plays in mice against bacterial strains of poor virulence. Deficiencies in the IFNg axis are not only associated with higher susceptibility to infection with Salmonella in mice but also with increased susceptibility to other intracellular pathogens (reviewed in Ref.…”