TUBERCULOSIS, SARCOIDOSIS AND HODGKINS-DISEASE - THEME WITH VARIATIONS

Apoptosis of infected macrophages is crucial for the resistance to int racellular pathogens: its failure leads to bacteria persistence and to iperactivated, long-lived, macrophages; further, persistent T cell ac tivation by infected macrophages may result in excessive cytokine secr etion, with local inflammation and tissue damage. Granulomata are trad itionally associated with the persistence of poorly degradable antigen s and are an almost stereotypical response shared by foreign bodies an d intracellular pathogens. We propose that the inability of macrophage s to undergo apoptosis after phagocytosis/infection may contribute to the pathogenesis of granulomatous diseases. In this review we analyze the molecular pathways that may underlie this defect, with particular attention to the interaction between CD95 and its ligand and to the ro le of nitric oxide, a double-edged mediator, able to cause both apopto sis and necrosis (Fund. Clin. Immunol. 3: 747-152, 1995).