International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 214 - GENE EXPRESSION PROFILING DURING THE EARLY HOST RESPONSE TO SALMONELLA INFECTION IN MICE

Salez L
Centre for the Study of Host Resistance, McGill University Health Center, Montreal General Hospital, Montréal, Québec, Canada

Co-Authors: 2) Bihl F, 1)3) Malo D.
Institutions: 2) Gén étique Expérimentale et Moléculaire, CNRS, Orléans, France, 3) Department of Human Genetics, McGill University, Montréal

Toll-like receptors (TLRs) are pattern recognition receptors involved in the detection of infectious pathogens and in modulating immune responses. Toll-like receptor 4 (Tlr4) is involved in the recognition of lipopolysaccharides (LPS), the main immunogenic molecule of the outer membrane of Gram-negative bacteria. We previously created four Tlr4 transgenic mice on a C57BL/10ScNCR Tlr4 null background to study the effect of Tlr4 expression on the host response to infection with the Gram-negative bacteria Salmonella enterica serovar Typhimurium. We have shown that over-expression of Tlr4 by itself has a survival advantage in transgenic mice early during infection. The beneficial effect of Tlr4 over-expression is greatly enhanced when the mice present a wild-type allele at Slc11a1 (solute carrier family 11 member 1), another critical innate immune gene involved in resistance to infection with Salmonella Typhimurium. Tlr4 and Nramp1 exhibit functional epistatic interaction to improve the capacity of the host to control bacterial replication. We are using gene expression profiling and quantitative PCR to study the impact of Tlr4 and Slc11a1 expression on the ability of the host to detect whole bacteria in vivo and induce inflammatory responses.


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