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Infect. Immun. doi:10.1128/IAI.01021-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Tissue Selective Proinflammatory Gene Induction in Mice Infected with Wild-Type Compared to DNA Adenine Methylase- or Flagella-deficient Salmonella

Department of Molecular, Cellular and Developmental Biology, University of California at Santa Barbara, Santa Barbara, CA 93106

^* To whom correspondence should be addressed. Email: samuel{at}lifesci.ucsb.edu.

	Abstract

Mutants of Salmonella enterica serovar Typhimurium deficient in DNA adenine methylase (Dam) are attenuated for virulence in mice and confer heightened immunity in vaccinated animals. In contrast, infection of mice with wild-type or flagellin deficient mutants of Salmonella causes typhoid fever. Here we examined the bacterial load and spatio-temporal kinetics of expression of several classes of host genes in Peyer's patches, liver and spleen following oral infection of mice with wild-type (WT), dam mutant or flagellin deficient (flhC) Salmonella. Genes evaluated included inflammatory (IL-1, TNF-), chemokine (MIP2), Th1/Th2 indicator (IL-12p40, IL-4), and interferon system (IFN-, IFN-, Mx, PKR, iNOS, SOCS1) beacons. We show that maximal IFN system and proinflammatory gene induction occurred by 5 days after infection and was comparable between WT and flhC strains, but significantly lower for the dam mutant. Additionally, host gene expression in systemic tissues of individual animals is dependent on the bacterial load in the Peyer's patches for mice infected with WT, dam, or flhC mutant Salmonella as early as 8 hours after infection. Moreover, a bacterial load threshold in the Peyer's patches is necessary to stimulate such host gene induction in the liver and spleen. Taken together, these results suggest that bacterial load and the accompanying strain-specific cytokine signature are important determinants of the host innate immune response and associated disease manifestations observed in dam as compared to WT and flhC Salmonella-infected animals.