巨噬细胞在眼部感染后限制单纯疱疹病毒1型生长中的作用。

Role of macrophages in restricting herpes simplex virus type 1 growth after ocular infection.

作者信息

Cheng H, Tumpey T M, Staats H F, van Rooijen N, Oakes J E, Lausch R N

机构信息

Department of Microbiology and Immunology, College of Medicine, University of South Alabama, Mobile, USA.

出版信息

Invest Ophthalmol Vis Sci. 2000 May;41(6):1402-9.

PMID:10798656

Abstract

PURPOSE

To investigate the role macrophages play in controlling herpes simplex virus (HSV)-1 replication after infection of the murine cornea.

METHODS

Macrophage depletion in selected tissues before or after virus infection was achieved by repeated subconjunctival (SCJ) and/or intravenous (IV) injection of liposomes containing dichloromethylene diphosphonate (L-Cl2MDP). Controls received liposomes containing phosphate-buffered saline (L-PBS). The efficiency of depletion was evaluated by histologic examination. Virus content in infected tissues was determined by standard plaque assay. Delayed-type hypersensitivity (DTH) responsiveness was assessed using the ear-swelling assay. Antibody isotype responses to virus antigens and cytokine production were monitored by enzyme-linked immunosorbent assay.

RESULTS

Balb/c mice given SCJ injection of L-Cl2MDP 4 and 2 days before HSV-1 corneal infection were found to have ocular virus titers as much as 10(5)-fold higher than that seen in the L-PBS-treated controls 8 days after infection. When L-Cl2MDP treatment was delayed until 2 and 4 days after infection, virus titers in the eye were analogous to those in the control animals. Subconjunctival and submandibular lymph node macrophages in mice given local (SCJ) L-Cl2MDP pretreatment were profoundly reduced, whereas the number of corneal Langerhans' cells and lymph node dendritic cells remained unchanged. Local L-Cl2MDP pretreatment was associated with significantly reduced DTH responsiveness to HSV-1 antigen, and an alteration in selected antibody isotype production. Depletion of macrophages in the subconjunctival tissue before corneal infection was not accompanied by enhanced virus growth at early times (2 or 4 days) after infection.

CONCLUSIONS

Macrophages play an important role in restricting HSV-1 growth after corneal infection. These cells appear to be required for the development of an acquired immune response, presumably by functioning in antigen processing and presentation. The hypothesis that macrophages are major participants in innate immunity to HSV-1 corneal infection was not supported.

摘要

目的

研究巨噬细胞在小鼠角膜感染单纯疱疹病毒1型（HSV-1）后对病毒复制的控制作用。

方法

通过反复结膜下（SCJ）和/或静脉内（IV）注射含二氯亚甲基二膦酸盐（L-Cl2MDP）的脂质体，在病毒感染之前或之后实现特定组织中巨噬细胞的清除。对照组接受含磷酸盐缓冲盐水（L-PBS）的脂质体。通过组织学检查评估清除效率。通过标准蚀斑试验测定感染组织中的病毒含量。使用耳部肿胀试验评估迟发型超敏反应（DTH）反应性。通过酶联免疫吸附测定监测对病毒抗原的抗体同种型反应和细胞因子产生。

结果

在HSV-1角膜感染前4天和2天接受SCJ注射L-Cl2MDP的Balb/c小鼠，在感染后8天，其眼内病毒滴度比L-PBS处理的对照组高10^5倍。当L-Cl2MDP治疗延迟至感染后2天和4天，眼内病毒滴度与对照动物相似。接受局部（SCJ）L-Cl2MDP预处理的小鼠结膜下和下颌下淋巴结巨噬细胞显著减少，而角膜朗格汉斯细胞和淋巴结树突状细胞数量保持不变。局部L-Cl2MDP预处理与对HSV-1抗原的DTH反应性显著降低以及选定抗体同种型产生的改变有关。角膜感染前结膜下组织中巨噬细胞的清除在感染后早期（2或4天）并未伴随病毒生长增强。