Role of macrophage scavenger receptors in response to Listeria monocytogenes infection in mice
Role of macrophage scavenger receptors in response to Listeria monocytogenes infection in mice
复制标题
DOI：
10.1016/s0002-9440(10)63956-9
复制
发表时间：
2001-01-01
影响因子：
6
通讯作者：
Kodama, T
中科院分区：
文献类型：
--
作者：
Ishiguro, T;Naito, M;Kodama, T
I型和II型巨噬细胞清道夫受体（SR-A I/II）识别多种聚阴离子，包括细菌细胞壁产物如脂多糖，表明SR-A I/II在针对细菌感染的免疫中的作用。SR-A I/II缺陷（MSR-A-/-）小鼠更易感染产溶血素-O（LLO）的单核细胞增生李斯特菌。感染后，野生型（MSR-A+/+）小鼠枯否细胞吞噬李斯特菌的数量明显高于MSR-A-/-小鼠，MSR-A-/-小鼠肝肉芽肿的数量和直径明显大于MSR-A+/+小鼠。与MSR-A +/+小鼠相比，单核细胞增生李斯特菌在MSR-A-/-小鼠的肝脏中以更高的水平复制，并且来自MSR-A-/-小鼠的巨噬细胞显示出体外杀死李斯特菌的能力受损。然而，来自MSR-A+/+和MSR-A-/-小鼠的巨噬细胞对具有失活LLO基因的同基因突变型单核细胞增多性李斯特菌显示出相似水平的杀李斯特菌活性。与未处理的MSR-A +/+巨噬细胞相比，用抗SE-A I/II抗体（2F 8）处理的MSR-A+/+巨噬细胞和MSR-A-/-巨噬细胞的吞噬活性显著受损，表明SR-A VII作为单核细胞增生李斯特菌的受体发挥功能。电镜观察显示，在体内和体外，大多数单核细胞增生李斯特菌已从MSR-A+/+巨噬细胞的溶酶体中清除。相比之下，单核细胞增生李斯特菌在吞噬体-溶酶体融合之前快速溶解吞噬体膜并逃逸到用2F 8处理的MSR-A-/-巨噬细胞和MSR-A+/+巨噬细胞中的胞质溶胶，这些发现表明，SR-A I/II在宿主防御真菌感染中起着至关重要的作用，不仅作为受体发挥作用，而且通过调节LLO-1介导杀李斯特菌机制。巨噬细胞的依赖性细胞逃逸。
Type I and type II macrophage scavenger receptors (SR-A I/II) recognize a variety of polyanions including bacterial cell-wall products such as lipopolysaccharide, suggesting a role for SR-A I/II in immunity against bacterial infection. SR-A I/II-defrcient (MSR-A-/-) mice were more susceptible to infection with listeriolysin-O (LLO)-producing Listeria monocytogenes. After infection, Kupffer cells in wild-type (MSR-A+/+) mice phagocytized larger numbers of Listeria than those in MSR-A-/- mice, The number and the diameter of hepatic granulomas were larger in MSR-A-/- mice than MSR-A+/+ mice. L, monocytogenes replicated at higher levels in the liver of MSR-A-/- mice compared with MSR-A+/+ mice, and macrophages from MSR-A-/- mice showed impaired ability to kill Listeria in vitro. However, macrophages from MSR-A+/+ and MSR-A-/- mice showed similar levels of listericidal activity against isogenic mutant L, monocytogenes with an inactivated LLO gene. The listerial phagocytic activities of MSR-A+/+ macrophages treated with an anti-SE-A I/II antibody (2F8) and MSR-A-/- macrophages were significantly impaired compared with untreated MSR-A+/+ macrophages, indicating that SR-A VII function as a receptor for L, monocytogenes. Electron microscopy revealed that most L, monocytogenes had been eliminated from the lysosomes of MSR-A+/+ macrophages in vivo and in vitro. In contrast, L, monocytogenes rapidly lysed the phagosomal membrane and escaped to the cytosol in MSR-A-/- macrophages and in MSR-A+/+ macrophages treated with 2F8 before phagosome-lysosome fusion, These findings imply that SR-A I/II plays a crucial role in host defense against listerial infection not only by functioning as a receptor but also by mediating listericidal mechanisms through the regulation of LLO-dependent listerial escape from the macrophages.