Koziel H, Eichbaum Q, Kruskal B A, Pinkston P, Rogers R A, Armstrong M Y, Richards F F, Rose R M, Ezekowitz R A
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
J Clin Invest. 1998 Oct 1;102(7):1332-44. doi: 10.1172/JCI560.
The macrophage mannose receptor, a pattern recognition molecule and component of innate immunity, mediates binding and phagocytosis of Pneumocystis carinii and likely represents an important clearance mechanism in the lungs of immunocompetent hosts. The purpose of this study was to examine the ability of alveolar macrophages from HIV-infected individuals to bind and phagocytose P. carinii, and to investigate the role of the macrophage mannose receptor in mediating this interaction. Compared with healthy individuals, alveolar macrophage phagocytosis of P. carinii from HIV+ persons was reduced up to 74% (P = 0.02), primarily reflecting a reduction in the number of organisms associated with each macrophage (P = 0.019). Furthermore, macrophages from HIV+ individuals demonstrated up to an 80% (P < 0.05) reduction in mannose receptor surface expression and endocytosis. Mannose receptor affinity was unaltered, and mRNA levels were modestly reduced (P < 0.05). Cells from HIV+ individuals with CD4(+) counts < 200 cells/mm3 (representing individuals at high clinical risk for P. carinii pneumonia) demonstrated the lowest levels of P. carinii phagocytosis and mannose receptor endocytosis. In vitro HIV infection of alveolar macrophages from healthy individuals reduced mannose receptor endocytosis to 53.2% (P < 0.05) and P. carinii binding and phagocytosis to 67.4% (P < 0.05) of control. Our studies suggest that HIV infection may alter innate immunity in the lungs, and that impaired alveolar macrophage mannose receptor-mediated binding and phagocytosis of P. carinii may contribute to the susceptibility of HIV-infected individuals to this opportunistic pulmonary pathogen.
巨噬细胞甘露糖受体是一种模式识别分子和固有免疫的组成部分，介导卡氏肺孢子虫的结合与吞噬，可能是免疫健全宿主肺内重要的清除机制。本研究旨在检测HIV感染个体的肺泡巨噬细胞结合和吞噬卡氏肺孢子虫的能力，并探讨巨噬细胞甘露糖受体在介导这种相互作用中的作用。与健康个体相比，HIV阳性者肺泡巨噬细胞对卡氏肺孢子虫的吞噬作用降低了74%（P = 0.02），这主要反映了与每个巨噬细胞相关的病原体数量减少（P = 0.019）。此外，HIV阳性个体的巨噬细胞甘露糖受体表面表达和内吞作用降低了80%（P < 0.05）。甘露糖受体亲和力未改变，mRNA水平略有降低（P < 0.05）。CD4(+)细胞计数< 200个细胞/mm3的HIV阳性个体的细胞（代表卡氏肺孢子虫肺炎临床高危个体）显示出最低水平的卡氏肺孢子虫吞噬作用和甘露糖受体内吞作用。对健康个体的肺泡巨噬细胞进行体外HIV感染后，甘露糖受体内吞作用降至对照组的53.2%（P < 0.05），卡氏肺孢子虫的结合和吞噬作用降至对照组的67.4%（P < 0.05）。我们的研究表明，HIV感染可能改变肺内的固有免疫，肺泡巨噬细胞甘露糖受体介导的卡氏肺孢子虫结合和吞噬受损可能导致HIV感染个体对这种机会性肺部病原体易感。
