title: Joint effects of host genetic background and mycobacterial pathogen on susceptibility to infection.
abstract: The present study examined the differential contribution of host genetic background and mycobacterial pathogen variability to biological and mechanistic phenotypes of infection. For this purpose, A/J and C57BL/6J mice were infected intravenously with a low dose of Mycobacterium tuberculosis H37Rv or the Russia, Japan, and Pasteur substrains of Mycobacterium bovis bacille Calmette-Guérin (BCG). The pulmonary bacterial counts (number of CFU) and transcript levels of select cytokines (e.g., Ifng, Il12b, and Il4) at 1, 3, and 6 weeks postinfection were measured as biological and mechanistic phenotypes, respectively. The individual and combined impact of the host and mycobacteria on these phenotypes was assessed using three-way analysis of variance (ANOVA), which partitions phenotypic variation into host, pathogen, time, and interaction effects. All phenotypes, except pulmonary Il4 transcript levels, displayed evidence for host-mycobacterium specificity by means of significant interaction terms. Pulmonary expression profiles of 34 chemokines and chemokine-related genes were compared across the hosts and mycobacteria. The differences in induction of these immune messenger genes between A/J and C57BL/6J mice were modest and generally failed to reach significance. In contrast, the mycobacteria induced significant variance in a subset of the immune messenger genes, which was more evident in A/J mice relative to that in C57BL/6J mice. Overall, the results demonstrated the importance of considering the joint effects of the mycobacterial and host genetic backgrounds on susceptibility to mycobacterial infections.
authors.affiliation: McGill Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Tania
authors.initials: T
authors.lastname: Di Pietrantonio
authors.forename: José A
authors.initials: JA
authors.lastname: Correa
authors.forename: Marianna
authors.initials: M
authors.lastname: Orlova
authors.forename: Marcel A
authors.initials: MA
authors.lastname: Behr
authors.forename: Erwin
authors.initials: E
authors.lastname: Schurr
mesh_terms: D000818:Animals; D058491:Bacterial Load; D004198:Disease Susceptibility / Q000382:microbiology; D020869:Gene Expression Profiling; D005798:Genes, Bacterial / Q000235:genetics; D007371:Interferon-gamma / Q000502:physiology; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000472:pathogenicity*; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D014376:Tuberculosis / Q000235:genetics* / Q000382:microbiology / Q000662:veterinary; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000382:microbiology
chemical_list: D007371:Interferon-gamma