Many bacterial pathogens are rapidly killed after being engulfed by bactericidal macrophages. Once in the phagosome, the phagosome quickly undergoes maturation by fusing with lysosomal compartments. Due to production of reactive oxygen and nitrogen species, as well as pH changes, bacteria are rapidly killed and degraded. However, a select subset of bacterial pathogens has evolved to evade this destruction and survive intracellularly. This can be accomplished by two different means. The first mechanism is by bacterial interference with phagosome maturation so that bacteria can reside within a vacuole. For example, Legionella injects proteins into the host cell via a type IV secretion system that interfere with normal cell trafficking, leading to creation of a protective vacuole (Roy 2002). Instead of containing endocytic markers on its membrane, ER and Golgi-derived proteins are present. Within this vacuole, Legionella can replicate and survive within the cell until nutrients are limited, and the Legionella lyse the cell for transmission to the next host cell. The second mechanism for bacterial evasion of phagosome-mediated killing is for the bacteria to escape from the phagosome before maturation. This is the case for L. monocytogenes as well as other cytosolic intracellular pathogens such as Shigella. After engulfment by macrophages, approximately 10% of L. monocytogenes escape from the phagosome before their destruction (de Chastellier and Berche 1994). This is accomplished by the expression of the virulence factors listeriolysin O (LLO), phosphatidylinositol-specific phospholipase C (PI-PLC), and phosphatidylcholine-preferring phospholipase C (PC-PLC) (see Chap. 9 for a detailed description of how these virulence factors mediate L. monocytogenes escape from the primary and secondary vacuoles).
Macrophages are not the only cell type within which L. monocytogenes resides. L. monocytogenes invasion of nonprofessional antigen presenting cells, such as hepatocytes and enterocytes, also contributes to the bacterium's evasion of the immune response since these cells have limited antigen presentation capacities compared to macrophages. L. monocytogenes expresses on its surface several different ligands that, upon binding with receptors on host cells, initiate a signaling cascade that leads to internalization of the bacterium (see Chap. 8 for a detailed description of this process). The best studied ligand-receptor engagement is between internalin and E-cadherin, which is important for tight-junction formation between enterocytes (Cossart et al. 2003). Expression of internalin on the surface of L. monocytogenes is necessary for bacterial entry into enterocytes (Gaillard et al. 1991, Mengaud et al. 1996). This interaction is very specific, since human E-cadherin, but not mouse E-cadherin, can serve as a receptor (Lecuit et al. 1999). This mechanism to enter nonphagocytic cells has allowed L. monocytogenes to gain a niche where they are not subjected to the harsh antimicrobial activities or to professional antigen presentation of macrophages.
Was this article helpful?