Milligan G N
Division of Infectious Diseases, Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
J Virol. 1999 Aug;73(8):6380-6. doi: 10.1128/JVI.73.8.6380-6386.1999.
Large numbers of polymorphonuclear leukocytes (PMNs) infiltrated the murine vaginal mucosa within 24 h after intravaginal inoculation with an attenuated strain of herpes simplex virus type 2 (HSV-2). The role of these cells in resolution of a primary genital infection and in protection of HSV-immune animals against challenge with a fully virulent HSV-2 strain was investigated. Depletion of greater than 95% of the PMNs at the vaginal mucosal surface prior to intravaginal inoculation with an attenuated HSV-2 strain resulted in significantly higher virus titers on days 3 to 7 but only slightly delayed resolution of the primary genital infection. These results suggest that neutrophils helped control the infection but that other immune mechanisms ultimately cleared the virus. Interestingly, depletion of PMNs from HSV-immune mice prior to challenge with a fully virulent HSV-2 strain resulted in a rise in virus titers to levels comparable to those of nonimmune mice and a more pronounced diminution of virus clearance from the vaginal mucosa despite the presence of HSV-specific B and T cells. Levels of gamma interferon (IFN-gamma) and HSV-specific antibody were comparable in neutrophil-depleted and control-treated immune mice following HSV-2 challenge, suggesting that RB6-8C5 treatment did not impair T- and B-cell function. Therefore, these results suggest that neutrophils play a role in limiting and clearing HSV-2 vaginal infections and that they are, in association with HSV-specific B and T cells, an important component in immune protection of the vaginal mucosa.
在经阴道接种2型单纯疱疹病毒(HSV-2)减毒株后24小时内,大量多形核白细胞(PMNs)浸润小鼠阴道黏膜。研究了这些细胞在原发性生殖器感染消退以及HSV免疫动物抵御完全毒力的HSV-2毒株攻击中的作用。在经阴道接种HSV-2减毒株之前,使阴道黏膜表面95%以上的PMNs耗竭,导致在第3至7天病毒滴度显著更高,但原发性生殖器感染的消退仅略有延迟。这些结果表明,中性粒细胞有助于控制感染,但其他免疫机制最终清除了病毒。有趣的是,在以完全毒力的HSV-2毒株攻击之前,从HSV免疫小鼠中耗竭PMNs,导致病毒滴度上升至与非免疫小鼠相当的水平,并且尽管存在HSV特异性B细胞和T细胞,从阴道黏膜清除病毒的能力却更明显地降低。在HSV-2攻击后,中性粒细胞耗竭的免疫小鼠和对照处理的免疫小鼠中γ干扰素(IFN-γ)水平和HSV特异性抗体水平相当,这表明RB6-8C5处理并未损害T细胞和B细胞功能。因此,这些结果表明中性粒细胞在限制和清除HSV-2阴道感染中发挥作用,并且它们与HSV特异性B细胞和T细胞一起,是阴道黏膜免疫保护的重要组成部分。