The implication of the Bcg locus in the control of natural resistance to infection with a live vaccine strain (LVS) of the intracellular pathogen Francisella tularensis was studied. Analysis of phenotypic expression of natural resistance and susceptibility was performed using mouse strains congenic at the Bcg locus. Comparison of the kinetics of bacterial colonization of spleen showed that B10.A.Bcg(r) mice were extremely susceptible during early phases of primary sublethal infection, while their congenic C57BL/10N [Bcg(s)] counterparts could be classified as resistant to F. tularensis LVS infection according to the 2-log-lower bacterial CFU within the tissue as long as 5 days after infection. Different phenotypes of Bcg congenic mice were associated with differential expression of the cytokines tumor necrosis factor alpha, interleukin-10, and gamma interferon and production of reactive oxygen intermediates. These results strongly suggest that the Bcg locus, which is close or identical to the Nramp1 gene, controls natural resistance to infection by F. tularensis and that its effect is the opposite of that observed for other Bcg-controlled pathogens.

• MeSH
• Cytokines biosynthesis   MeSH
• Nitrites metabolism   MeSH
• Cells, Cultured MeSH
• Chromosome Mapping * MeSH
• Membrane Proteins genetics   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Immunity, Innate MeSH
• Cation Transport Proteins * MeSH
• Reactive Oxygen Species MeSH
• Spleen microbiology   MeSH
• Carrier Proteins genetics   MeSH
• Tularemia immunology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cytokines MeSH
• Nitrites MeSH
• Membrane Proteins MeSH
• natural resistance-associated macrophage protein 1 MeSH Browser
• Cation Transport Proteins * MeSH
• Reactive Oxygen Species MeSH
• Carrier Proteins MeSH