title: Host immune response to Salmonella enterica serovar Typhimurium infection in mice derived from wild strains.
abstract: Studies of mouse models of endotoxemia and sepsis with gram-negative bacteria have shown that the host response is genetically controlled. Mice infected with the gram-negative bacterium Salmonella enterica serovar Typhimurium exhibit marked genetic differences in disease manifestation, and the wild-derived strain Mus musculus molossinus MOLF/Ei is extremely susceptible to S. enterica serovar Typhimurium. The kinetics of bacterial proliferation within the liver and the spleen and histological examination of tissue sections have suggested that MOLF/Ei mice do not succumb to infection because of overwhelming bacterial growth in the reticuloendothelial organs or massive tissue necrosis, as observed in other Salmonella-susceptible strains. MOLF/Ei mice respond normally to lipopolysaccharide (LPS) in vivo and in vitro, as determined by the production of tumor necrosis factor alpha and spleen cell mitogenesis. However, they have a unique cytokine profile in response to infection compared to that observed for other Salmonella-susceptible mice. There was increased expression of mRNA of the interleukin-1 alpha (IL-1 alpha) and IL-1 beta genes as the infection in the spleens and livers of MOLF/Ei mice progressed. Despite the fact that MOLF/Ei mice have the ability to respond to LPS and the fact that there are significant increases in IL-1 alpha and IL-1 beta mRNA, Nos2 in the spleen is not upregulated and nitrite production by spleen cells is reduced. At the central level, the inflammatory response is characterized by strong upregulation of the inhibitory factor kappa B alpha and Toll-like receptor 2 genes, two genes known to be regulated by LPS and IL-1 in the brain. The high levels of IL-1 expression in the spleens and livers of MOLF/Ei mice may have important implications for the activation of peripheral and central innate immune mechanisms.
authors.affiliation: Department of Biochemistry, McGill University, Montréal, Québec, Canada H3G 1A4.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Sebastiani
authors.forename: Véronique
authors.initials: V
authors.lastname: Blais
authors.forename: Vanessa
authors.initials: V
authors.lastname: Sancho
authors.forename: Stefanie N
authors.initials: SN
authors.lastname: Vogel
authors.forename: Mary M
authors.initials: MM
authors.lastname: Stevenson
authors.forename: Philippe
authors.initials: P
authors.lastname: Gros
authors.forename: Jean-Martin
authors.initials: JM
authors.lastname: Lapointe
authors.forename: Serge
authors.initials: S
authors.lastname: Rivest
authors.forename: Danielle
authors.initials: D
authors.lastname: Malo
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility; D029721:Drosophila Proteins; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000235:genetics; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000473:pathology; D012486:Salmonella typhimurium / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
chemical_list: D016207:Cytokines; D029721:Drosophila Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse