Influence of the Bcg locus on natural resistance to primary infection withthe facultative intracellular bacterium Francisella tularensis in mice

The implication of the Bcg locus in the control of natural resistance to in fection with a live vaccine strain (LVS) of the intracellular pathogen Fran cisella tularensis was studied. Analysis of phenotypic expression of natura l resistance and susceptibility was performed using mouse strains congenic at the Beg locus. Comparison of the kinetics of bacterial colonization of s pleen 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 inf ection 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 fac tor alpha, interleukin-10, and gamma interferon and production of reactive oxygen intermediates. These results strongly suggest that the Bcg locus, wh ich is close or identical to the Nramp1 gene, controls natural resistance t o infection by F. tularensis and that its effect is the opposite of that ob served for other Bcg-controlled pathogens.