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Refinement of the genetics of the host response to Salmonella infection in MOLF/Ei: regulation of type 1 IFN and TRP3 pathways by Ity2

Genes & Immunity volume 13, pages 175–183 (2012)Cite this article

Abstract

Typhoid fever, which is caused by Salmonella typhi and paratyphi, is a severe systemic disease that remains a major public health issue in several areas of the world. We can model the human disease using mice infected with a related bacterium, Salmonella typhimurium. This model recapitulates several clinical aspects of the human disease and allows for the study of the host response to Salmonella typhimurium infection in vivo. Previous work in our laboratory has identified three Immunity to typhimurium loci (Ity, Ity2 and Ity3) in the wild-derived MOLF/Ei mice, influencing survival after infection with Salmonella typhimurium. The MOLF/Ei alleles at Ity and Ity2 are protective, while the MOLF/Ei allele at Ity3 confers susceptibility. In this paper, we have generated a novel cross combination between the highly susceptible strain, MOLF/Ei, and the resistant strain, 129S6, to better define the genetic architecture of susceptibility to infection in MOLF/Ei. Using this cross, we have replicated the locus on chr 11 (Ity2) and identified a novel locus on chr 13 (Ity13). Using microarrays and transcriptional profiling, we examined the response of uninfected and infected Ity2 congenic mice. These analyses demonstrate a role for both type-1-interferon (IFN) and TRP53 signaling in the pathogenesis of Salmonella infection.

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Acknowledgements

We wish to acknowledge the technical assistance of Nadia Prud’homme, Line Larivière and Melissa Herman and the contribution of the McGill University and Génome Québec Functional Genomics platform personnel and the Innovation Centre. We thank Dr Shauna Dauphinee for critical reading of this manuscript. This work was supported by the Canadian Institutes of Health Research (to DM). RK is a recipient of a Fonds de la Recherche en Santé du Québec Studentship. DM is a McGill Dawson Scholar.

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Authors and Affiliations

  1. Department of Human Genetics, McGill University, Montréal, Québec, Canada

    R Khan & D Malo

  2. Université Paris René Descartes, Necker Medical School, Paris, France

    V Sancho-Shimizu

  3. Department of Medicine, McGill University, Montréal, Québec, Canada

    C Prendergast & D Malo

  4. Department of Veterinary Clinical and Diagnostic Sciences, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada

    M-F Roy

  5. Memorial University of Newfoundland, St John's, Newfoundland, Canada

    J-C Loredo-Osti

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  2. V Sancho-Shimizu
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Correspondence to D Malo.

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Khan, R., Sancho-Shimizu, V., Prendergast, C. et al. Refinement of the genetics of the host response to Salmonella infection in MOLF/Ei: regulation of type 1 IFN and TRP3 pathways by Ity2. Genes Immun 13, 175–183 (2012). https://doi.org/10.1038/gene.2011.69

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