Host Genes and Resistance/Sensitivity to Military Priority Pathogens

Abstract : This report provides data from our study of differential susceptibility to DoD priority pathogens (Francisella tularensis (FT), Burkholderia pseudomallei (Bp), Acinetobacter baumannii (Ab), Leishmania major (Lm), SARS, H5N1 avian influenza) using BXD recombinant inbred mice. The FT project identified phenotypes that correlate with differential immune response to pneumonic infections. The Ab project has identified clear phenotypic differences between the innate immune responsiveness of B6 and D2 mice to pulmonary infection. The Bp project has identified QTLs linked with differential susceptibility to pneumonic Bp infection. The SARS project found difference in susceptibility to MA15 virus infection between B6 and D2 mouse strains. The influenza project has identified a significant QTL associated with early production of proinflammatory cytokines on Chr 6. The Lm project has identified two suggestive loci on Chr 12 and 15 regulating parasite burden. The mouse genomics core generated datasets for different mouse strains (available on www.genenetwork.org). The Bioinformatics (Modeling core) analyzed biological data from projects using Bayesian network analysis and created a Bayesian Network Webserver. The Chlamydia genetic studies in BXD mice was used as the prototype model. The bioinformatics core used this model to develop and integrate the algorithms for testing pathways underlying host responses to pathogen infections.