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Innate interferon response in macrophage and epithelial cells infected with wild-type compared to DNA adenine methylase and flagellin mutant Salmonella enterica serovar Typhimurium.

Simon R, Samuel CE

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

Salmonella enterica serovar Typhimurium is highly virulent and mediates robust interferon (IFN)-stimulated gene (ISG) induction, whereas bacterial mutants that lack the DNA adenine methylase (Dam) are attenuated, elicit a reduced ISG activation profile, and establish immunity to murine typhoid fever. We show here that in contrast to observations in mice, infection of macrophage cell cultures with either wild-type (WT) or dam(-) mutant Salmonella resulted in surprisingly similar kinetics and amplitudes of induction of IFN-beta, the type I IFN-alpha,beta beacon gene Mx, and the type II IFN-gamma beacon inducible nitric oxide synthase (iNOS). Likewise, activation of NF-kappaB-dependent gene expression in epithelial cells was comparable with WT and dam(-) mutant Salmonella. In contrast, the flagellin-deficient flhC(-) mutant did not activate NF-kappaB in epithelial cells but activated ISG expression comparable to that of WT Salmonella in macrophage cells. WT and dam(-) strains displayed a similar Toll-like receptor 5 (TLR5)-dependent NF-kappaB activation, whereas the flhC(-) mutant lacked this activity. UV-inactivated Salmonella elicited similar ISG induction to that of viable Salmonella in macrophages and mediated the establishment of a functional antiviral state but displayed decreased cytocidal activity. These results establish that the inherent IFN system-inducing capacities of dam(-) and WT Salmonella strains in cultured macrophage and epithelial cells, unlike the mouse, are indistinguishable.

Published 4 May 2007 in J Interferon Cytokine Res, 27(4): 317-27.
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