Pathomorphogenesis of tubercular histologic changes: mechanisms of granuloma formation, maintenance and necrosis

Abstract

The histopathological hallmark of infections with Mycobacterium tuberculosis is the development of centrally necrotizing granulomatous lesions. Granulomas are focal accumulations of mononuclear cells in various states of differentiation, in which the local activation of mycobacteria-infected macrophages by specific T cells takes place. On the one hand, this assures efficient containment of mycobacterial growth and demarcation of the infectious focus. On the other hand this is associated with the displacement of and irreversible damage to functionally vital organ tissue (predominantly in the lungs). New insights, emerging from animal models of infection, into the dynamic mechanisms regulating the induction, maintenance and caseation of tuberculous granulomas explain why highly effective anti-inflammatory therapies, e. g. administration of anti-TNF monoclonal antibodies, may result in reactivation of tuberculosis.