Wellcome Trust Centre for Cell-Matrix Research, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, United Kingdom.
School of Biological Sciences, Faculty of Biology, Medicine, and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, United Kingdom.
Proc Natl Acad Sci U S A. 2018 Jan 23;115(4):726-731. doi: 10.1073/pnas.1713539115. Epub 2018 Jan 8.
Mucosal surfaces represent critical routes for entry and exit of pathogens. As such, animals have evolved strategies to combat infection at these sites, in particular the production of mucus to prevent attachment and to promote subsequent movement of the mucus/microbe away from the underlying epithelial surface. Using biochemical, biophysical, and infection studies, we have investigated the host protective properties of the skin mucus barrier of the tadpole. Specifically, we have characterized the major structural component of the barrier and shown that it is a mucin glycoprotein (Otogelin-like or Otogl) with similar sequence, domain organization, and structural properties to human gel-forming mucins. This mucin forms the structural basis of a surface barrier (∼6 μm thick), which is depleted through knockdown of Otogl. Crucially, Otogl knockdown leads to susceptibility to infection by the opportunistic pathogen To more accurately reflect its structure, tissue localization, and function, we have renamed Otogl as Skin Mucin, or MucXS. Our findings characterize an accessible and tractable model system to define mucus barrier function and host-microbe interactions.
黏膜表面是病原体进入和退出的关键途径。因此，动物进化出了在这些部位对抗感染的策略，特别是产生黏液以防止附着，并促进随后的黏液/微生物从上皮表面移动。我们使用生化、生物物理和感染研究方法，研究了 蝌蚪皮肤黏液屏障的宿主保护特性。具体来说，我们已经描述了屏障的主要结构成分，并表明它是一种粘蛋白糖蛋白（Otogelin 样或 Otogl），具有与人类凝胶形成粘蛋白相似的序列、结构域组织和结构特性。这种粘蛋白构成了表面屏障的结构基础（厚约 6 微米），通过敲低 Otogl 而被耗尽。至关重要的是，Otogl 敲低会导致对机会性病原体 的易感性。为了更准确地反映其结构、组织定位和功能，我们将 Otogl 重新命名为 皮肤粘蛋白，或 MucXS。我们的发现描述了一个易于接近和易于处理的模型系统，用于定义黏液屏障功能和宿主-微生物相互作用。
