FEATURE ARTICLE
Pathogens, Host-Cell Invasion and Disease
Invading pathogens can co-opt even the cells of the immune system. New anti-infective drugs may arise from an understanding of this chemical warfare
Erich Gulbins, Florian Lang
Invasion: Getting In
The immune system can detect alien organisms only outside cells or on the cell surface. This leaves the system vulnerable to attack from within its own cells. For instance, Shigella flexneri, a bacterium that infects people through feces-contaminated food and causes severe diarrhea and vomiting, first attaches to and then penetrates macrophages—immune cells that are specialized in devouring invading pathogens—as they patrol the intestines. Shigella multiplies inside the host cell, where it is unchallenged by the immune system. Eventually, the infected macrophage dies and releases new bacteria that spread to and infect nearby epithelial cells and cause destruction of the intestinal tissue.
Listeria monocytogenes, a bacterium that causes meningitis and spontaneous abortion in pregnant women, first infects epithelial cells in the intestinal tract as it is taken up with contaminated food. The bacteria multiply and cross the epithelium to the bloodstream. It is in the blood that they penetrate the patient's immune cells, which then carry the infection all over the body. If those infected cells get into the brain and release the Listeria, they can cause meningitis, a life-threatening infection of the brain's surrounding membrane. If the infected cells travel through the placenta of a pregnant woman and release the pathogen in the fetus, the subsequent infection can kill the unborn child.
Another natural target is the lining of cells on the surface of the intestines or the lungs, another of the body's natural barriers against infectious microorganisms. All surfaces that are exposed to the outside—the skin, the intestines, the respiratory and urinary tracts—are lined with epithelial cells that are so tightly interconnected that no virus or bacterium can squeeze through. In addition, these surfaces are covered with immune cells ready to attack any invading alien structure. Many pathogens therefore infect these cells first to establish a bridgehead from which they can release their progeny into the tissues and blood vessels that lie on the other, inner side of the epithelial barrier. The bloodstream may then become the medium through which they can spread throughout the body and infect other tissues and organs.
Pathogens have evolved a wide variety of mechanisms and strategies that enable them to enter body cells. However, a pathogen's invasion of a target cell often requires the active participation of the host. Indeed, the internalization of a pathogen involves the concerted interplay of many bacterial and host-cell proteins, and also involves the plasma membrane, the outer membrane that surrounds the host cell. The challenge for a pathogen, similar to the problem faced by a burglar cracking a safe, is to find a chemical code that starts the processes that eventually lead to its internalization by the host cell.
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