Hu Jianzhang, Hu Yingfeng, Chen Shikun, Dong Chenhuan, Zhang Jingjin, Li Yanling, Yang Juan, Han Xiaoli, Zhu Xuejun, Xu Guoxing
The Eye Center of the First Affiliated Hospital of Fujian Medical University, Fujian Eye Institute, 20 Chazhong Road, Fuzhou 350005, China.
The Eye Center of the First Affiliated Hospital of Fujian Medical University, Fujian Eye Institute, 20 Chazhong Road, Fuzhou 350005, China.
Exp Eye Res. 2014 Dec;129:57-65. doi: 10.1016/j.exer.2014.10.014. Epub 2014 Oct 18.
Macrophages under the conjunctival tissue are the first line defender cells of the corneas. Elimination of these cells would lead to aggravation of fungal keratitis. To determine how the course of fungal keratitis would be altered after the activation of these macrophages, a murine model was achieved by intrastromal instillation of latex beads before the corneas were infected with Fusarium solani. The keratitis was observed and clinically scored daily. Infected corneas were homogenized for colony counts. The levels of the IL-12, IL-4, MPO, MIF and iNOS cytokines were measured in the corneas using real-time polymerase chain reactions and enzyme-linked immunosorbent assays. CD3+, CD4+ and CD8+ lymphocytes in the corneas, submaxillary lymph nodes and peripheral blood were detected using immunohistochemistry and flow cytometry, respectively. The latex bead-treated mice exhibited aggravated keratitis. Substantially increased macrophage and polymorphonuclear leukocyte infiltration was detected in the corneas, although few colonies were observed. There was a marked increase in the IL-12, IL-4, MPO, MIF and iNOS expression in the corneas. The numbers of CD3+, CD4+ and CD8+ lymphocytes and the CD4+/CD8+ ratio were significantly enhanced in the corneas and submaxillary lymph nodes. However, the number of CD4+ lymphocytes was decreased in the peripheral blood, while the number of CD8+ lymphocytes increased. Collectively, our data demonstrate that the activation of macrophages in the cornea may cause an excessive immune response. Macrophages appear to play a critical role in regulating the immune response to corneal infections with F. solani.
结膜组织下的巨噬细胞是角膜的第一道防线防御细胞。消除这些细胞会导致真菌性角膜炎加重。为了确定这些巨噬细胞被激活后真菌性角膜炎的病程会如何改变，在角膜被茄病镰刀菌感染之前，通过基质内滴注乳胶珠建立了小鼠模型。每天观察角膜炎情况并进行临床评分。将感染的角膜匀浆进行菌落计数。使用实时聚合酶链反应和酶联免疫吸附测定法测量角膜中白细胞介素 -12、白细胞介素 -4、髓过氧化物酶、巨噬细胞移动抑制因子和诱导型一氧化氮合酶细胞因子的水平。分别使用免疫组织化学和流式细胞术检测角膜、颌下淋巴结和外周血中的CD3 +、CD4 +和CD8 +淋巴细胞。经乳胶珠处理的小鼠表现出加重的角膜炎。尽管观察到的菌落很少，但在角膜中检测到巨噬细胞和多形核白细胞浸润显著增加。角膜中白细胞介素 -12、白细胞介素 -4、髓过氧化物酶、巨噬细胞移动抑制因子和诱导型一氧化氮合酶的表达明显增加。角膜和颌下淋巴结中CD3 +、CD4 +和CD8 +淋巴细胞的数量以及CD4 + / CD8 +比值显著增加。然而，外周血中CD4 +淋巴细胞数量减少，而CD8 +淋巴细胞数量增加。总体而言，我们的数据表明角膜中巨噬细胞的激活可能导致过度的免疫反应。巨噬细胞似乎在调节对茄病镰刀菌角膜感染的免疫反应中起关键作用。
