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Cellular resistance in experimental murine tularemia

McGill University
Publication Date
  • Health Sciences
  • Immunology.


A murine model of host resistance to infection with Francisella tularensis, live vaccine strain, has been established. This facultative intracellular bacterium causes in mice an acute infection which lasts for approximately 12 days. Resistance to infection is associated with the appearance in the spleens of cells with the ability to transfer anti-tularemic resistance to naive mice, a response which is maximal 7 days following infection. Depletion of B cells does not compromise the ability of immune cells to transfer resistance. Treatment of mice with immune serum prior to infection leads to an increased hepatic and decreased splenic growth of Francisella. This effect is attributable to a serum-induced shift in the organ uptake of Francisella from the spleen to the liver. Acquired anti-tularemic resistance is critically dependent upon T lymphocytes, as evidenced by the inability of T lymphocyte-depleted immune cells to transfer resistance, and by the increased susceptibility to infection in mice treated with the T cell immunosuppressant, cyclosporin A. The passive transfer of resistance is mediated mainly by T cells bearing the L3T4 marker, but Lyt 2$ sp{+}$ cells may also play a minor role. Macrophages are essential to the control of Francisella infection, since inhibition of the functional activity of this cell population by silica injection leads to a decrease in the ability of mice to contain bacterial growth. The interactions between T cells and macrophages leading to the expression of anti-tularemic immunity are restricted by the product of the I-A region of the H-2 complex. Resistance to tularemia is influenced by the genetic background of the host. Among inbred mouse strains, several levels of resistance to infection are evident. Genetic analysis of resistance/susceptibility to tularemia in F$ sb1$ and F$ sb2$ hybrid mice, and in recombinant inbred strains of mice derived from resistant and susceptible progenitor strains, indicated that the inheritance pat

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