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Chapter 27 : Immunogenetics of the Host Response to Bacteria in Mice

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Abstract:

This chapter presents an overview of the specific mouse loci identified as playing a key role in susceptibility to infection with human bacterial pathogens. The role of natural resistance-associated macrophage protein 1 (Nramp1) in host defenses against clinically relevant strains of and was addressed in genetic studies in humans from areas of endemic tuberculosis (The Gambia) and leprosy (South Vietnam) infection, using informative markers derived from the NRAMP1 gene region. Mice bearing naturally occurring (Nramp1) or experimentally induced (Nramp1) mutations at Nramp1 are extremely susceptible to intravenous or subcutaneous infection with low doses of serovar (10 CFU), with uncontrolled bacterial replication in the spleen and liver of susceptible mice leading to uniform death within 4 to 5 days of infection. induces apoptosis during infection of permissive human macrophages and in alveolar epithelial cell lines. Avirulent mutants cannot induce either apoptosis or caspase 3 activation, and specific inhibition of caspase 3 activity can block both -induced apoptosis and cytopathogenicity. Hence, it seems likely that the number of described susceptibility and resistance loci for divergent bacterial infections in the mouse will increase dramatically over the coming years.

Citation: Gros P, Schurr E. 2002. Immunogenetics of the Host Response to Bacteria in Mice, p 407-420. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch27

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