Immune-mediated phagocytosis and killing of Streptococcus pneumoniae are associated with direct and bystander macrophage apoptosis
Immune-mediated phagocytosis and killing of Streptococcus pneumoniae are associated with direct and bystander macrophage apoptosis
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DOI：
10.1086/323084
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发表时间：
2001-09-15
影响因子：
6.4
通讯作者：
Read, RC
中科院分区：
文献类型：
--
作者：
Dockrell, DH;Lee, M;Read, RC
巨噬细胞的凋亡可能是病原体导向的免疫逃逸机制，也可能是宿主对感染的适当反应。健康供者的人单核细胞来源的巨噬细胞(C-MDM)呈现低水平的结构性凋亡，但与I型肺炎链球菌(I-MDM)共同培养20h后，MDM的凋亡率显著增加。I-MDM的凋亡与细菌的吞噬和细胞内杀伤有关，这种作用可被caspase抑制剂z-VAD-fmk阻断，但不能被Fas阻断的抗体阻断。多聚甲醛固定的I-MDM诱导未感染的同基因单核细胞的凋亡水平高于单独孵育或与固定的C-MDM孵育的单核细胞。抗Fas抗体可阻断同基因单核细胞的凋亡。巨噬细胞对肺炎链球菌的免疫反应包括一种与成功吞噬和杀菌有关的新的凋亡形式。在宿主对肺炎链球菌的成功反应中，体内的这种反应可能调节对感染的炎症反应。
Apoptosis of macrophages may be a pathogen-directed mechanism of immune escape or may represent appropriate host response to infection. Human monocyte-derived macrophages (MDMs) from healthy donors (C-MDMs) exhibited low-level constitutive apoptosis, but culture of MDMs with opsonized serotype I Streptococcus pneumoniae (I-MDMs) for 20 h resulted in significantly increased apoptosis. I-MDM apoptosis was associated with phagocytosis of bacteria and intracellular killing that was blocked by the caspase inhibitor z-VAD-fmk but not by Fas-blocking antibody. Paraformaldehyde-fixed I-MDMs induced apoptosis in uninfected syngeneic monocytes at levels greater than those in monocytes incubated alone or incubated with fixed C-MDMs. Apoptosis of syngeneic monocytes was blocked by anti-Fas antibody. The immune response of macrophages to S. pneumoniae includes a novel form of apoptosis that is associated with successful phagocytosis and bacterial killing. This response in vivo may regulate the inflammatory response to infection during a successful host response against S. pneumoniae.