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Tlr5 is not primarily associated with susceptibility to Salmonella Typhimurium infection in MOLF/Ei mice

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Abstract

The extreme susceptibility to infection with Salmonella Typhimurium of wild-derived MOLF/Ei mice has been linked to one genomic region on Chromosome 1 (Ity3). A member of the Toll-like receptors family, Tlr5, located on distal Chromosome 1, was previously shown to be a candidate gene for Ity3 based on expression studies and sequencing analysis. The candidacy of Tlr5 as a Salmonella-susceptibility gene was evaluated functionally by comparing Tlr5 C57BL/6J and MOLF/Ei alleles in vitro and in vivo. In vitro studies showed that the MOLF/Ei Tlr5 allele is more transcriptionally active when the gene is removed from its natural genomic environment. This observation was supported by in vivo studies in B6.MOLF-Ity3 congenic mice that showed that mice homozygous for the MOLF/Ei allele at Ity3, including Tlr5, had an increased response to flagellin as measured by IL-6 and CXCL-1 secretion in the serum compared with parental MOLF/Ei mice. Despite the fact that both MOLF/Ei and B6.MOLF-Ity/Ity3 mice are more susceptible to Salmonella Typhimurium infection than B6.MOLF-Ity mice, they exhibit a different phenotype with respect to Tlr5 expression and Tlr5 signaling, supporting the prediction that Tlr5 is not primarily involved in the disease phenotype underlying the Ity3 locus in MOLF/Ei mice.

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Acknowledgments

The authors thank Line Lariviere for excellent technical services and Silvia Vidal for helpful discussions. This work was supported by grants from the Canadian Institutes of Health Research (CIHR) and the Howard Hughes Medical Institute (HHMI). D.M. is a scholar of CIHR and an International Research Scholar of the HHMI.

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Authors and Affiliations

  1. Department of Human Genetics, McGill University, Montreal, Quebec, Canada, H3G 1A4

    Isabelle Angers, Vanessa Sancho-Shimizu & Danielle Malo

  2. Center for the Study of Host Resistance, McGill University Health Center, Montreal, Quebec, Canada, H3G 1A4

    Isabelle Angers, Vanessa Sancho-Shimizu & Danielle Malo

  3. INRS-Institut Armand-Frappier, Laval, Quebec, Canada, H7V 1B7

    Albert Descoteaux

  4. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, 30322, USA

    Andrew T. Gewirtz

  5. Department of Medicine, McGill University, Montreal, Quebec, Canada, H3G 1A4

    Danielle Malo

  6. Center for the Study of Host Resistance, Montreal General Hospital, Room L11-144, Montréal, Québec, H3G 1A4, Canada

    Danielle Malo

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  1. Isabelle Angers
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  2. Vanessa Sancho-Shimizu
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  3. Albert Descoteaux
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  4. Andrew T. Gewirtz
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  5. Danielle Malo
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Correspondence to Danielle Malo.

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Isabelle Angers and Vanessa Sancho this authors contributed equally to this work.

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Angers, I., Sancho-Shimizu, V., Descoteaux, A. et al. Tlr5 is not primarily associated with susceptibility to Salmonella Typhimurium infection in MOLF/Ei mice. Mamm Genome 17, 385–397 (2006). https://doi.org/10.1007/s00335-005-0132-x

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  • DOI: https://doi.org/10.1007/s00335-005-0132-x

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