Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, Virginia, USA.
Department of Pathology, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.
Infect Immun. 2019 Mar 25;87(4). doi: 10.1128/IAI.00646-18. Print 2019 Apr.
Studies have implicated as an important etiological agent in bacterial vaginosis (BV). It produces a cholesterol-dependent cytolysin, vaginolysin (VLY). In this study, we sought to characterize the interaction between vaginal epithelium, , and VLY using EpiVaginal tissues from MatTek. These tissues are three-dimensional and have distinct apical and basolateral sides, enabling comparison of the effects of and VLY following exposure to either side. We measured cytotoxicity, cytokine production, and bacterial growth, following apical versus basolateral exposure. exhibited more-rapid growth in coculture with the tissue model when it was exposed to the apical side. VLY permeabilized cells on the basolateral side of the tissues but failed to permeabilize apical epithelial cells. Cytokine secretion in response to VLY and also depended on the polarity of exposure. VLY did not cause significant changes in cytokine levels when exposed apically. Apical tissue challenge by appeared to dampen the inflammatory response, as decreases in granulocyte-macrophage colony-stimulating factor (GM-CSF) (6.6-fold), RANTES (14.8-fold), and interferon gamma inducible protein 10 kDa (IP-10) (53-fold) and an increase in interleukin-1 receptor antagonist (IL-1ra) (5-fold) were observed. , normally colonizes the apical face of the vaginal epithelium. Results from this study suggest that while may grow on the apical face of the vaginal epithelium, its VLY toxin does not target these cells in this model. This phenomenon could have important implications regarding colonization of the vagina by and may suggest an explanation for the lack of an overt immune response to this organism.
研究表明， 是细菌性阴道病（BV）的重要病因。它产生一种胆固醇依赖性细胞毒素，即阴道溶素（VLY）。在这项研究中，我们试图利用 MatTek 的 EpiVaginal 组织来描述阴道上皮细胞、 和 VLY 之间的相互作用。这些组织是三维的，具有明显的顶端和基底外侧，能够比较 和 VLY 在暴露于任一侧后的影响。我们测量了细胞毒性、细胞因子产生和细菌生长，分别在顶端和基底外侧暴露后进行。当暴露于顶端时， 在与组织模型的共培养中表现出更快的生长。VLY 能够透化组织基底外侧的细胞，但不能透化顶端上皮细胞。对 VLY 和 的反应引起的细胞因子分泌也取决于暴露的极性。当暴露于顶端时，VLY 不会导致细胞因子水平发生显著变化。顶端组织对 的挑战似乎抑制了炎症反应，因为粒细胞-巨噬细胞集落刺激因子 (GM-CSF) (6.6 倍)、调节激活正常 T 细胞表达和分泌细胞因子 (RANTES) (14.8 倍) 和干扰素γ诱导蛋白 10kDa (IP-10) (53 倍) 的减少和白细胞介素-1 受体拮抗剂 (IL-1ra) (5 倍) 的增加。 通常定植在阴道上皮的顶端表面。这项研究的结果表明，虽然 可能在阴道上皮的顶端定植，但在这个模型中，其 VLY 毒素并不针对这些细胞。这种现象可能对 对阴道的定植具有重要意义，并且可能对缺乏对这种生物体的明显免疫反应提供了一种解释。
