Pulmonary tuberculosis: a comparative immunopathological investigation

Abstract

Inhalation of Mycobacterium tuberculosis precipitates an elaborate cascade of immunopathological events within the lung. The prototypical lesion is the granuloma, marked by a zonal accumulation of epithelioid macrophages, necrosis, fibrosis and a varied lymphocyte population. The containment or progression of the disease is controlled by a multiplicity of factors, but principally by the macrophages and lymphocytes and the cytokines that they secrete. How these elements are arranged both temporally and spatially in the infected lung however is poorly understood.In a series of in vivo experiments, inbred mice and outbred guinea pigs were experimentally incoulated with a low dose aerosol of Mycobacterium tuberculosis. We followed the growth of bacteria in the lungs alongside the development of the granulomas. Using histological, immunohistochemical, morphometric and flow cytometric analyses, special attention was paid to the arrangement of the lymphocyte subsets and the overall morphology of the lesion. This information was then applied to field studies, where pulmonary lesions of M. bovis infected European badgers, New Zealand brushtail possums and cattle were compared to each other and to the laboratory animals.We found that the temporal and spatial arrangement of lymphocytes, in particular the CD4+ and CD8+ T cell subsets differed markedly both within and between species. The morphology of the granuloma was also similarly diverse.Collectively, these data suggest that the immune response in the lungs to Mycobacterium tuberculosis infection depends not only on activation of specific immune cell populations, but also on the number and arrangement of primed T cells that reach the site of infection.