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Herpes simplex virus-binding IgG traps HSV in human cervicovaginal mucus across the menstrual cycle and diverse vaginal microbial composition.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2018-07-09 , DOI: 10.1038/s41385-018-0054-z
Holly A Schroeder 1 , Kenetta L Nunn 1, 2 , Alison Schaefer 1 , Christine E Henry 1 , Felix Lam 1 , Michael H Pauly 3 , Kevin J Whaley 3 , Larry Zeitlin 3 , Mike S Humphrys 4 , Jacques Ravel 4, 5 , Samuel K Lai 1, 2
Affiliation  

IgG possesses an important yet little recognized effector function in mucus. IgG bound to viral surface can immobilize otherwise readily diffusive viruses to the mucin matrix, excluding them from contacting target cells and facilitating their elimination by natural mucus clearance mechanisms. Cervicovaginal mucus (CVM) is populated by a microbial community, and its viscoelastic and barrier properties can vary substantially not only across the menstrual cycle, but also in women with distinct microbiota. How these variations impact the "muco-trapping" effector function of IgGs remains poorly understood. Here we obtained multiple fresh, undiluted CVM specimens (n = 82 unique specimens) from six women over time, and employed high-resolution multiple particle tracking to quantify the mobility of fluorescent Herpes Simplex Viruses (HSV-1) in CVM treated with different HSV-1-binding IgG. The IgG trapping potency was then correlated to the menstrual cycle, and the vaginal microbial composition was determined by 16 s rRNA. In the specimens studied, both polyclonal and monoclonal HSV-1-binding IgG appeared to consistently and effectively trap HSV-1 in CVM obtained at different times of the menstrual cycle and containing a diverse spectrum of commensals, including G. vaginalis-dominant microbiota. Our findings underscore the potential broad utility of this "muco-trapping" effector function of IgG to reinforce the vaginal mucosal defense, and motivates further investigation of passive immunization of the vagina as a strategy to protect against vaginally transmitted infections.

中文翻译:

单纯疱疹病毒结合 IgG 在整个月经周期和多种阴道微生物组成中将 HSV 捕获在人宫颈阴道粘液中。

IgG 在粘液中具有重要但鲜为人知的效应子功能。与病毒表面结合的 IgG 可以将原本容易扩散的病毒固定到粘蛋白基质上,阻止它们接触靶细胞并促进它们通过自然粘液清除机制消除。宫颈阴道粘液 (CVM) 中充满了微生物群落,其粘弹性和屏障特性不仅在月经周期内有很大差异,而且在具有不同微生物群的女性中也有很大差异。这些变异如何影响 IgG 的“黏膜捕获”效应子功能仍然知之甚少。在这里,随着时间的推移,我们从六名女性那里获得了多个新鲜的、未稀释的 CVM 标本(n = 82 个独特的标本),并采用高分辨率多粒子跟踪来量化荧光单纯疱疹病毒 (HSV-1) 在用不同 HSV-1 结合 IgG 处理的 CVM 中的移动性。然后将 IgG 捕获效力与月经​​周期相关联,并通过 16 s rRNA 确定阴道微生物组成。在所研究的标本中,多克隆和单克隆 HSV-1 结合 IgG 似乎始终有效地将 HSV-1 捕获在 CVM 中,这些 CVM 在月经周期的不同时间获得,并且含有多种共生菌,包括 G. vaginalis 显性微生物群。我们的研究结果强调了 IgG 的这种“粘膜捕获”效应子功能在加强阴道粘膜防御方面的潜在广泛用途,
更新日期:2018-07-10
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