ABSTRACT

Complement receptor 3 (CD11b/CD18) is an important receptor that mediates adhesion, phagocytosis and chemotaxis in various immunocytes. The conidia of the medically-important pathogenic fungus, Aspergillus fumigatus can be internalized into alveolar epithelial cells to disseminate its infection in immunocompromised host; however, the role of CR3 in this process is poorly understood. In the present study, we investigated the potential role of CR3 on A. fumigatus internalization into type II alveolar epithelial cells and its effect on host intracellular PA content induced by A. fumigatus. We found that CR3 is expressed in alveolar epithelial cells and that human serum and bronchoalveolar lavage fluid (BALF) could improve A. fumigatus conidial internalization into A549 type II alveolar epithelial cell line and mouse primary alveolar epithelial cells, which were significantly inhibited by the complement C3 quencher and CD11b-blocking antibody. Serum-opsonization of swollen conidia, but not resting conidia led to the increase of cellular phosphatidic acid (PA) in A549 cells during infection. Moreover, both conidial internalization and induced PA production were interfered by CD11b-blocking antibody and dependent on FAK activity, but not Syk in alveolar epithelial cells. Overall, our results revealed that CR3 is a critical modulator of Aspergillus fumigatus internalization into alveolar epithelial cells.

摘要

补体受体 3 (CD11b/CD18) 是一种重要的受体，在各种免疫细胞中介导粘附、吞噬作用和趋化性。医学上重要的病原真菌烟曲霉的分生孢子可以内化到肺泡上皮细胞中，在免疫功能低下的宿主中传播其感染；然而，人们对 CR3 在这个过程中的作用知之甚少。在本研究中，我们研究了 CR3 在烟曲霉内化到 II 型肺泡上皮细胞中的潜在作用及其对烟曲霉诱导的宿主细胞内 PA 含量的影响。我们发现 CR3 在肺泡上皮细胞中表达，人血清和支气管肺泡灌洗液 (BALF) 可以改善烟曲霉分生孢子内化为 A549 II 型肺泡上皮细胞系和小鼠原代肺泡上皮细胞，这些细胞被补体 C3 猝灭剂和 CD11b 阻断抗体显着抑制。肿胀分生孢子的血清调理作用，而不是静息分生孢子，导致感染期间 A549 细胞中细胞磷脂酸 (PA) 的增加。此外，分生孢子内化和诱导的 PA 产生都受到 CD11b 阻断抗体的干扰，并且依赖于 FAK 活性，但不依赖于肺泡上皮细胞中的 Syk。总体而言，我们的研究结果表明，CR3 是烟曲霉内化进入肺泡上皮细胞的关键调节剂。