McCaw Shannon E, Schneider Jutta, Liao Edward H, Zimmermann Wolfgang, Gray-Owen Scott D
Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Canada.
Mol Microbiol. 2003 Aug;49(3):623-37. doi: 10.1046/j.1365-2958.2003.03591.x.
Gonorrhea is characterized by a purulent urethral or cervical discharge consisting primarily of neutrophils associated with Neisseria gonorrhoeae. These interactions are facilitated by gonococcal colony opacity-associated (Opa) protein binding to host cellular CEACAM receptors. Of these, CEACAM3 is restricted to neutrophils and contains an immunoreceptor tyrosine-based activation motif (ITAM) reminiscent of that found within certain phagocytic Fc receptors. CEACAM3 was tyrosine phosphorylated by a Src family kinase-dependent process upon infection by gonococci expressing CEACAM-specific Opa proteins. This phosphorylation was necessary for efficient bacterial uptake; however, a less efficient uptake process became evident when kinase inhibitors or mutagenesis of the ITAM were used to prevent phosphorylation. Ligated CEACAM3 was recruited to a cytoskeleton-containing fraction, intense foci of polymerized actin were evident where bacteria attached to HeLa-CEACAM3, and disruption of polymerized actin by cytochalasin D blocked all bacterial uptake by these cells. These data support a model whereby CEACAM3 can mediate the Opa-dependent uptake of N. gonorrhoeae via either an efficient, ITAM phosphorylation-dependent process that resembles phagocytosis or a less efficient, tyrosine phosphorylation-independent mechanism.
淋病的特征是尿道或宫颈脓性分泌物，主要由与淋病奈瑟菌相关的中性粒细胞组成。淋球菌菌落不透明相关（Opa）蛋白与宿主细胞CEACAM受体结合促进了这些相互作用。其中，CEACAM3局限于中性粒细胞，含有基于免疫受体酪氨酸的激活基序（ITAM），类似于某些吞噬性Fc受体中的ITAM。当被表达CEACAM特异性Opa蛋白的淋球菌感染时，CEACAM3通过Src家族激酶依赖性过程发生酪氨酸磷酸化。这种磷酸化对于有效摄取细菌是必要的；然而，当使用激酶抑制剂或ITAM诱变来阻止磷酸化时，一种效率较低的摄取过程变得明显。连接的CEACAM3被募集到含有细胞骨架的部分，在细菌附着于HeLa-CEACAM3的地方可见聚合肌动蛋白的强烈聚集，用细胞松弛素D破坏聚合肌动蛋白可阻止这些细胞对所有细菌的摄取。这些数据支持了一个模型，即CEACAM3可以通过类似于吞噬作用的高效、ITAM磷酸化依赖性过程或效率较低的酪氨酸磷酸化非依赖性机制介导淋病奈瑟菌的Opa依赖性摄取。
