Influence of theBcgLocus on Natural Resistance to Primary Infection with the Facultative Intracellular BacteriumFrancisella tularensisin Mice

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Abstract
The implication of theBcglocus in the control of natural resistance to infection with a live vaccine strain (LVS) of the intracellular pathogenFrancisella tularensiswas studied. Analysis of phenotypic expression of natural resistance and susceptibility was performed using mouse strains congenic at theBcglocus. 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 toF. tularensisLVS infection according to the 2-log-lower bacterial CFU within the tissue as long as 5 days after infection. Different phenotypes ofBcgcongenic 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 theBcglocus, which is close or identical to theNramp1gene, controls natural resistance to infection byF. tularensisand that its effect is the opposite of that observed for otherBcg-controlled pathogens.