Morphometric analysis of Mycobacterium tuberculosis infection in mice suggests a genetic influence on the generation of the granulomatous inflammatory response

Abstract

There is evidence in natural human disease and experimental infection in mice that host genetic factors influence susceptibility to infection with Mycobacterium tuberculosis and the progress of the disease. In mouse models, both H‐2 and non‐H‐2 genes have been implicated. In this study, four inbred strains of mice (Balb/b, Balb/k, B10, B10.BR), selected for combinations of two different H‐2 haplotypes on two different non‐H‐2 backgrounds, were inoculated with M. tuberculosis, strain H37Rv, by intraperitoneal injection. The histological features of the granulomatous inflammatory response in the liver and lungs were investigated during the first 18 weeks of the infection. Granuloma fraction, mean granuloma area, bacillary load, and the density of acid‐fast bacilli within granulomata were measured. Animals of all four strains showed the same general pattern of infection with an early, and later self‐limiting, infection of the liver and delayed onset, but progressive, infection of the lung. The non‐H‐2 related genetic background appears to influence the morphology of the granulomatous inflammatory response. In comparison, H‐2 differences appeared to be small and inconsistent.