MACROPHAGE APOPTOSIS IN MICROBIAL INFECTIONS

Upon infection with a pathogen, eukaryotic cells can undergo programme d cell death as an ultimate response. Therefore, modulation of apoptos is is often a prerequisite to establish a host-pathogen relationship. Some pathogens kill macrophages by inducing apoptosis and thus overcom e the microbicidal arsenal of the phagocyte. Apoptotic macrophages, on the other hand, can elicit an inflammation by secretion of proinflamm atory cytokines. Shigella flexneri, the aetiological agent of bacillar y dysentery, induces apoptosis in macrophages which, in agony, specifi cally release mature interleukin-1 beta (IL-1 beta). This cytokine att racts neutrophils (PMN) to the site of infection resulting in the mass ive colonic inflammation characteristic of bacillary dysentery. Shigel losis represents a paradigm of a proinflammatory apoptosis in a bacter ial infection. The molecular link between apoptosis and inflammation i s interleukin-1 beta converting enzyme (ICE) which is activated during macrophage apoptosis and binds to IpaB, a secreted Shigella protein.