Influence of Slc11a1 on the Outcome ofSalmonella entericaSerovar Enteritidis Infection in Mice Is Associated with Th Polarization

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Abstract
Genetic analyses identifiedSes1as a significant quantitative trait locus influencing the carrier state of 129S6 mice following a sublethal challenge withSalmonella entericaserovar Enteritidis. Previous studies have determined thatSlc11a1was an excellent candidate gene forSes1. Kinetics of infection in 129S6 mice andSlc11a1-deficient (129S6-Slc11a1tm1Mcg) mice demonstrated that the wild-type allele ofSlc11a1contributed to theS. entericaserovar Enteritidis carrier state as early as 7 days postinfection. Gene expression profiling demonstrated that 129S6 mice had a significant up-regulation of proinflammatory genes associated with macrophage activation at day 10 postinfection, followed by a gradual increase in immunoglobulin transcripts, whereas 129S6-Slc11a1tm1Mcgmice had higher levels of immunoglobulins earlier in the infection. Quantitative reverse transcription-PCR revealed an increase in Th1 cytokine (IfngandIl12) and Th1-specific transcription factorTbx21expression during infection in both the 129S6 and 129S6-Slc11a1tm1Mcgstrains. However, the expression ofGata3, a transcription factor involved in Th2 polarization,Cd28, andIl4was markedly increased inSlc11a1-deficient mice during infection, suggesting a predominant Th2 phenotype in 129S6-Slc11a1tm1Mcganimals followingS. entericaserovar Enteritidis infection. A strong immunoglobulin G2a response, reflecting Th1 activity, was observed only in 129S6 mice. All together, these results are consistent with an impact ofSlc11a1on Th cell differentiation during chronicS. entericaserovar Enteritidis infection. The presence of a Th2 bias inSlc11a1-deficient mice is associated with improved bacterial clearance.

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