Relationship of survival, organism containment, and granuloma formation inacute murine tuberculosis

The relationship among organism growth, immunopathology, and survival was s tudied in C57BL/6 and A/J mice acutely infected with Mycobacterium tubercul osis (MTB) (Erdman), Although organisms grew at similar rates in the lungs of both mouse strains, A/J mice died prior to 14 days after infection, wher eas C57BL/6 mice survived twice as long. The lungs of A/J mice exhibited ne crotizing interstitial inflammation and widely distributed acid-fast bacill i without granuloma formation. In contrast, the lungs of C57BL/6 mice had r elatively mild interstitial inflammation, which was replaced by focal granu lomas, and acid-fast bacilli were primarily within granulomas. MTB induced similar granulomas for A/J and C57BL/6 mice in spleen and liver. In the lun g, the A/J mice produced only transient messages for interferon-gamma (IFN- gamma), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-al pha), IL-10, and inducible nitric oxide synthase (iNOS), The C57BL/6 mice, in contrast, produced a delayed but sustained response in the lung correlat ing with granuloma onset and characterized by high induction of IL-6, IFN-g amma, IL-1 beta, IL-10, and TNF-alpha, Responses in the liver and spleen we re also evaluated. These results demonstrate that histopathology and cytoki ne response to MTB infection varies among organs in mice, Increased surviva l during acute infection may, therefore, depend on the ability to contain o rganisms within granulomas in the lung.