17 Induction of Apoptosis by Microbial Pathogens

Morphology of thymocytes undergoing necrosis and apoptosis. (A) Thymocytes undergoing necrosis. Organelles are critically damaged, the plasma membrane is ruptured, the cytoplasmic elements are dispersed, the shape of the nucleus is normally conserved, but flocculation of chromatin can be detected. (B) Thymocytes undergoing apoptosis. Cell shrinkage, blebbing at the cell surface, intense cytoplasmic vacuolization, conservation of organelle structure, condensation of the chromatin at the perinuclear region, and loss of nuclear morphology, which appears like segmentation of the nucleus, are all apparent.

Models for induction of apoptosis. Receptor binding or DNA damage activates a signal cascade that culminates in caspase activation and/or disruption of binding of members of the Bcl-2 family and release of mitochondrial proteins required for cell death.

Model of Shigella pathogenesis. (A) Colonic macrophages are activated to synthesize IL-1β by exposure to bacterial products of the normal microflora, like lipopolysaccharide (LPS). (B) Shigella translocates through M cells, infects resident macrophages, and escapes the phagocytic vacuoles. It secretes IpaB, which binds to ICE, which is activated. ICE activation leads to macrophage apoptosis and IL-1β maturation. IL-1β initiates an acute inflammatory response. (C) PMNs break the epithelial barrier, allowing further bacterial invasion. Bacteria invade epithelial cells through the basolateral side and then spread from cell to cell. Redrawn from A. Zychlinsky and P. J. Sansonetti, Trends Microbiol. 5:201–204, 1997.