The role of macrophage cell death in tuberculosis

Studies of host responses to infection have traditionally focused on the di rect antimicrobial activity of effector molecules (antibodies, complement, defensins, reactive oxygen and nitrogen intermediates) and immunocytes (mac rophages, lymphocytes, and neutrophils among others). The discovery of the systems for programmed cell death of eukaryotic cells has revealed a unique role for this process in the complex interplay between microorganisms and their cellular targets or responding immunocytes, In particular, cells of t he monocyte/macrophage lineage have been demonstrated to undergo apoptosis following intracellular infection with certain pathogens that are otherwise capable of surviving within the hostile environment of the phagosome or wh ich can escape the phagosome. Mycobacterium tuberculosis is a prototypical 'intracellular parasite' of macrophages, and the direct induction of macrop hage apoptosis by this organism has recently been reported from several lab oratories. This paper reviews the current understanding of the mechanism an d regulation of macrophage apoptosis in response to M. tuberculosis and exa mines the role this process plays in protective immunity and microbial viru lence.