Aderem A, Underhill D M
Department of Immunology, University of Washington, Seattle 98195, USA.
Annu Rev Immunol. 1999;17:593-623. doi: 10.1146/annurev.immunol.17.1.593.
Phagocytosis of pathogens by macrophages initiates the innate immune response, which in turn orchestrates the adaptive response. In order to discriminate between infectious agents and self, macrophages have evolved a restricted number of phagocytic receptors, like the mannose receptor, that recognize conserved motifs on pathogens. Pathogens are also phagocytosed by complement receptors after relatively nonspecific opsonization with complement and by Fc receptors after specific opsonization with antibodies. All these receptors induce rearrangements in the actin cytoskeleton that lead to the internalization of the particle. However, important differences in the molecular mechanisms underlying phagocytosis by different receptors are now being appreciated. These include differences in the cytoskeletal elements that mediate ingestion, differences in vacuole maturation, and differences in inflammatory responses. Infectious agents, such as M. tuberculosis, Legionella pneumophila, and Salmonella typhimurium, enter macrophages via heterogeneous pathways and modify vacuolar maturation in a manner that favors their survival. Macrophages also play an important role in the recognition and clearance of apoptotic cells; a notable feature of this process is the absence of an inflammatory response.
巨噬细胞对病原体的吞噬作用启动了固有免疫反应，进而协调适应性免疫反应。为了区分感染因子和自身成分，巨噬细胞进化出了数量有限的吞噬受体，如甘露糖受体，该受体可识别病原体上的保守基序。病原体在被补体进行相对非特异性调理后，也可通过补体受体被吞噬；在被抗体进行特异性调理后，可通过Fc受体被吞噬。所有这些受体都会诱导肌动蛋白细胞骨架重排，从而导致颗粒内化。然而，现在人们认识到不同受体介导吞噬作用的分子机制存在重要差异。这些差异包括介导摄取的细胞骨架成分不同、液泡成熟过程不同以及炎症反应不同。诸如结核分枝杆菌、嗜肺军团菌和鼠伤寒沙门氏菌等感染因子通过多种途径进入巨噬细胞，并以有利于其存活的方式改变液泡成熟过程。巨噬细胞在识别和清除凋亡细胞方面也发挥着重要作用；这一过程的一个显著特点是不存在炎症反应。
