IgG in cervicovaginal mucus traps HSV and prevents vaginal herpes infections.
IgG in cervicovaginal mucus traps HSV and prevents vaginal herpes infections.
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IgG是宫颈阴道粘液（CVM）中的主要免疫球蛋白，但粘液中的IgG如何保护免受感染尚未完全了解。IgG通过宫颈粘液迅速扩散，仅因与粘蛋白的短暂粘附相互作用而稍微减慢。我们假设这种几乎不受阻碍的扩散允许IgG在病原体表面上快速积累，并且所得的IgG阵列与粘液凝胶形成多个弱粘附性交联，从而有效地捕获（捕获）病原体，防止它们引发感染。在这里，我们报告单纯疱疹病毒血清型1（HSV-1）容易穿透新鲜的，pH值中和的离体样品的CVM与低或没有检测到的抗HSV-1 IgG水平，但被困在样品中，甚至适度水平的抗HSV-1 IgG。在含有少量或不含内源性抗HSV-1 IgG的样品中，加入外源性抗HSV-1 IgG，从静脉注射免疫球蛋白中亲和纯化，捕获浓度低于中和所需浓度的病毒粒子，并具有与内源性IgG相似的效价。将纯化的抗HSV-1 IgG去糖基化或去除其Fc组分，显著降低了捕获效力。最后，针对HSV-gG的非中和IgG显著保护小鼠免受阴道感染，并且通过温和灌洗去除阴道粘液消除保护。这些观察结果表明，IgG-Fc具有聚糖依赖性“粘膜捕获”效应子功能，可在粘膜表面提供异常有效的保护。
IgG is the predominant immunoglobulin in cervicovaginal mucus (CVM), yet how IgG in mucus can protect against infections is not fully understood. IgG diffuses rapidly through cervical mucus, slowed only slightly by transient adhesive interactions with mucins. We hypothesize this almost unhindered diffusion allows IgG to accumulate rapidly on pathogen surfaces, and the resulting IgG array forms multiple weak adhesive crosslinks to mucus gel that effectively trap (immobilize) pathogens, preventing them from initiating infections. Here, we report herpes simplex virus serotype 1 (HSV-1) readily penetrated fresh, pH-neutralized ex vivo samples of CVM with low or no detectable levels of anti-HSV-1 IgG, but was trapped in samples with even modest levels of anti-HSV-1 IgG. In samples with little or no endogenous anti-HSV-1 IgG, addition of exogenous anti-HSV-1 IgG, affinity purified from intravenous immunoglobulin, trapped virions at concentrations below those needed for neutralization and with similar potency as endogenous IgG. Deglycosylating purified anti-HSV-1 IgG, or removing its Fc component, markedly reduced trapping potency. Finally, a non-neutralizing IgG against HSV-gG significantly protected mice against vaginal infection, and removing vaginal mucus by gentle lavage abolished protection. These observations suggest IgG-Fc has a glycan dependent “muco-trapping” effector function that may provide exceptionally potent protection at mucosal surfaces.