Natural killer cells and the biology of parasitism

Publisher Summary Parasites constitute many different forms of microbes, with various sizes, routes of infection, and life-stages within the mammalian host. Parasites are able to grow and persist within their hosts, with no benefit to the host. The hallmark of parasite persistence within an immune-competent host is the ability of parasites to avoid clearance by the host immune system without causing the host to succumb to infection. This necessitates a delicate balance between parasite immune-evasion mechanisms and the generation of host immunity to the parasite. While metazoan parasites are multicellular, extracellular organisms, many protozoan parasites are intracellular or have intracellular phases during infection of mammalian hosts. Many protozoan parasites invade host cells or tissue, replicate, and then lyse their host cells to disseminate the parasite to new tissues, either locally or systemically through the blood or lymphatic system. One innate immune effector, the natural killer (NK) cell, can recognize and destroy pathogen-infected or malignant cells. NK cells circulate through the blood, spleen and peripheral organs, such as the liver, and express germ-line-encoded activating and inhibitory receptors. NK cells may also play a role in pathophysiology when parasite persistence leads to chronic disease. Metazoan parasites, commonly called helminthes, may use NK cells to help establish infection, although in several cases NK cells seem to contribute to parasite control. NK cells play a variety of roles in parasite infection either directly through interactions with parasites or parasite-infected cells, or indirectly through cytokine secretion, predominately through interferon-gamma (IFN-γ). In terms of immune control, NK cells can play a primary role as first responders in the innate immune system and influence adaptive immune responses.