Innate interferon response in macrophage and epithelial cells infected with wild-type compared to DNA adenine methylase and flagellin mutant Salmonella enterica serovar Typhimurium.
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.
Simon
Raphael
R
Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.
Samuel
Charles E
CE
D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D005408:Flagellin / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007109:Immunity / Q000502:physiology*; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D051379:Mice; D064547:Myxovirus Resistance Proteins; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000235:genetics / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000378:metabolism
C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; D016328:NF-kappa B; D051198:Toll-Like Receptor 5; D005408:Flagellin; D016899:Interferon-beta; D052247:Nitric Oxide Synthase Type II; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); D019204:GTP-Binding Proteins