Complement receptor type 3 (CD11b/CD18) involvement is essential for killing of Listeria monocytogenes by mouse macrophages.
Complement receptor type 3 (CD11b/CD18) involvement is essential for killing of Listeria monocytogenes by mouse macrophages.
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DOI：
10.4049/jimmunol.151.10.5431
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发表时间：
1993-11
影响因子：
4.4
通讯作者：
D. Drevets;P. Leenen;P. Campbell
中科院分区：
文献类型：
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作者：
D. Drevets;P. Leenen;P. Campbell
最近的研究表明，C受体3型（CR3）介导了小鼠巨噬细胞对兼性单核增生李斯特菌的大部分吞噬作用，并能将其杀死。相反，非李斯特菌性巨噬细胞群体对李斯特菌的吞噬作用在很大程度上与cr3无关。这些发现表明，吞噬过程中CR3的结合可能是决定巨噬细胞是否杀死李斯特菌或被细菌寄生的重要因素。这里报告的实验验证了这一假设。将吞噬和杀伤分别进行分析，正常情况下具有李斯特菌杀灭能力的腹腔巨噬细胞仍能进行一定程度的吞噬，但当CR3被单抗阻断后，其杀灭李斯特菌的活性丧失。Anti-CR3 mAb以剂量依赖的方式抑制杀伤，并且在高剂量下细胞成为允许宿主。在吞噬和杀伤过程中缺乏活性C组分时，杀微生物功能也受到抑制。由于李斯特菌在李斯特性巨噬细胞中局限于吞噬体，而在非李斯特性巨噬细胞中逃逸到细胞质中，我们测试了抗cr3单抗是否能增强吞噬体逃逸。事实上，在对照和抗cr3单抗处理的巨噬细胞中，李斯特菌逃逸到细胞质中是罕见的。此外，这些细胞的电子显微镜显示分裂的噬菌体内细菌。综上所述，这些结果表明，在吞噬过程中与CR3的结合导致细菌死亡，而当与CR3的结合被阻断时，所参与的吞噬途径不会触发杀微生物活性。此外，在没有CR3参与的情况下，李斯特菌对吞噬体的限制本身并不足以使巨噬细胞具有李斯特菌杀灭活性。
Recent work indicated that C receptor type 3 (CR3) mediates most phagocytosis of the facultative intracellular bacterium Listeria monocytogenes by mouse macrophages, which can kill it. In contrast, phagocytosis of Listeria by a population of nonlistericidal macrophages was largely CR3-independent. These findings suggested that CR3 binding during phagocytosis may be important in determining whether a macrophage kills Listeria, or is parasitized by the bacterium. The experiments reported here tested this hypothesis. When phagocytosis and killing were assayed separately, normally listericidal peritoneal macrophages still could phagocytose to some extent, but lost listericidal activity when CR3 was blocked by mAb. Anti-CR3 mAb inhibited killing in a dose-dependent fashion, and at high doses the cells became permissive hosts. Microbicidal function also was inhibited when active C components were absent during phagocytosis and during killing. Because Listeria are confined to phagosomes in listericidal macrophages but escape into the cytoplasm in nonlistericidal macrophages, we tested whether anti-CR3 mAb enhanced phagosomal escape. In fact, escape of Listeria into the cytoplasm was rare in both control and anti-CR3 mAb-treated macrophages. Moreover, electron microscopy of these cells demonstrated dividing intraphagosomal bacteria. Taken together, these results suggest that binding to CR3 during phagocytosis leads to bacterial killing, and that phagocytic pathways engaged when binding to CR3 is blocked do not trigger microbicidal activity. Furthermore, restriction of Listeria to the phagosome in the absence of CR3 engagement is not by itself sufficient for macrophage listericidal activity.