A second pathway by which bacteria can invade nonphagocytic cells is known as the trigger mechanism (Figure 23–19B). It is used by various pathogens that cause food poisoning, including Salmonella enterica, and it is initiated when the bacterium injects a set of effector molecules into the host-cell cytosol through a type III secretion system (see Figure 23–7). Some of these effector molecules activate Rho family proteins, which in turn stimulate actin polymerization, as just discussed. Other bacterial effector proteins interact with host-cell cytoskeletal elements more directly, nucleating and stabilizing actin filaments and causing the rearrangement of actin cross-linking proteins. The overall effect is to cause the formation of localized ruffles on the surface of the host cell (Figure 23–19C and D), which fold over and engulf the bacteria by a process that resembles macropinocytosis. The appearance of cells being invaded by use of the trigger mechanism invasin receptors type III secretioninvasin (integrins, cadherins) apparatus is similar to the ruffling induced by some extracellular growth factors, suggesting that the bacteria exploit normal intracellular signaling pathways.
The uptake of viruses and bacteria into host cells is carried out largely by the host, with the pathogen being a relatively passive participant. In contrast, intracellular eukaryotic parasites, which are typically much larger than other types of intracellular pathogens, invade host cells through a variety of complex pathways that usually require energy expenditure by the parasite.
Toxoplasma gondii,a cat parasite that also causes occasional serious human infections, is an example. When this protozoan contacts a host cell, it protrudes an unusual microtubule-based structure called a conoid, which facilitates entry into the host cell (Figure 23–20). The energy for invasion seems to come from actin polymerization in the parasite rather than host cytoskeleton, and invasion also requires at least one unusual parasite myosin motor protein (Class XIV; see Figure 16–40). At the point of contact, the parasite discharges effector proteins from secretory organelles into the host cell, and these proteins target various host pathways to enable invasion, to block an innate immune response, and promote survival. As the parasite moves into the host cell, a membrane derived from the host-cell plasma membrane surrounds it. Remarkably, the parasite removes host transmembrane proteins from the surrounding membrane as it forms, so that the parasite is protected in a membrane-enclosed compartment that does not fuse with lysosomes and does not participate in host-cell membrane trafficking processes (see Figure 23–20). The specialized membrane is selectively porous: it allows the parasite to take up small metabolic intermediates and nutrients from the host cell’s cytosol but excludes macromolecules. Malaria parasites invade human red blood cells using a similar mechanism.
Figure 23–19 Mechanisms used by bacteria to induce phagocytosis by host cells that are normally nonphagocytic.
In the zipper mechanism, bacteria express an invasion protein that binds with high affinity to a host-cell receptor, which is often a cell–cell or cell–matrix adhesion protein. (B) In the trigger mechanism, bacteria inject a set of effector molecules into the host-cell cytosol through a type III secretion system called SPI1 (Salmonella pathogenicity island 1), inducing membrane ruffling. Both the zipper and trigger mechanisms cause the polymerization of actin at the site of bacterial attachment by activating Rho family small GTPases and the Arp 2/3 complex. (C) A scanning electron micrograph showing a very early stage of Salmonella enterica invasion by the trigger mechanism. Bacteria (pseudocolored yellow) are shown surrounded by a small membrane ruffle.