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Infection and Immunity, April 2002, p. 1997-2009, Vol. 70, No. 4
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.4.1997-2009.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Host Immune Response to Salmonella enterica Serovar Typhimurium Infection in Mice Derived from Wild Strains

Departments of Biochemistry,¹ Human Genetics,⁴ Medicine, McGill University, Montréal, Canada H3G 1A4,⁶ Centre for the Study of Host Resistance, McGill University Health Centre,² Faculté de Médecine Vétérinaire, Université de Montréal, Montreal, Canada J2S 7C6,⁷ Centre Hospitalier de l'Université Laval Research Center and Department of Anatomy and Physiology, Laval University, Québec, Canada G1V 4G2,³ Uniformed Services University of Health Science, Bethesda, Maryland 20814⁵

Received 31 July 2001/ Returned for modification 5 November 2001/ Accepted 4 January 2002

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 (IL-1) and IL-1ß 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 and IL-1ß 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.

Editor: R. N. Moore

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