Enteric Pathogens and Their Toxin-Induced Disruption of the Intestinal Barrier through Alteration of Tight Junctions in Chickens.
Enteric Pathogens and Their Toxin-Induced Disruption of the Intestinal Barrier through Alteration of Tight Junctions in Chickens.
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DOI：
10.3390/toxins9020060
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发表时间：
2017-02-10
期刊：
影响因子：
4.2
通讯作者：
Hess M
中科院分区：
文献类型：
--
作者：
Awad WA;Hess C;Hess M
保持健康的肠道环境是可持续动物生产的先决条件。肠道在营养物质的消化和吸收中起着关键作用，并构成了影响鸟类健康的外部因素的初始器官。肠上皮屏障作为宿主和管腔环境之间的第一道防线。它由连续单层的肠上皮细胞组成，通过细胞间连接复合物连接，使相邻细胞之间的空间缩小。因此，防止了溶质和水通过细胞旁途径的自由通过。紧密连接（TJs）是多蛋白复合物，其对于上皮屏障的完整性和功能至关重要，因为它们不仅连接细胞，而且形成允许细胞之间渗透的通道，从而导致不同紧密性的上皮表面。紧密连接的分子组成、超微结构和功能受到生理和病理刺激的不同调节。体内和体外研究均表明，紧密连接完整性的降低极大地导致通常称为“肠漏”的病症。屏障完整性的丧失允许管腔抗原（微生物、毒素）通过粘膜移位进入全身，这些抗原通常被排除在外，随后破坏肠粘膜稳态，同时增加对全身感染、慢性炎症和吸收不良的易感性。大量证据表明，肠道屏障功能障碍是导致某些肠道细菌致病的重要因素。研究表明，某些肠道病原体可通过改变其毒素介导的紧密连接蛋白来诱导肠道上皮细胞的通透性缺陷。解决微生物用于劫持紧密连接功能的策略对于我们理解微生物发病机制是重要的，因为一些病原体可以利用紧密连接蛋白作为受体用于附着和随后的内化，而其他病原体通过不同的途径修饰或破坏紧密连接蛋白，从而提供通往底层组织的通道。本文就紧密连接的结构和功能及其在鸡肠道细菌致病中的作用作一综述。一个主要的结论是，肠道病原体破坏鸡上皮屏障功能的分子机制需要更好地理解，明确强调空肠弯曲菌，沙门氏菌和产气荚膜梭菌。这是一个要求，以帮助发现新的策略，以避免肠道屏障的损害或尽量减少感染的后果。
Maintaining a healthy gut environment is a prerequisite for sustainable animal production. The gut plays a key role in the digestion and absorption of nutrients and constitutes an initial organ exposed to external factors influencing bird’s health. The intestinal epithelial barrier serves as the first line of defense between the host and the luminal environment. It consists of a continuous monolayer of intestinal epithelial cells connected by intercellular junctional complexes which shrink the space between adjacent cells. Consequently, free passing of solutes and water via the paracellular pathway is prevented. Tight junctions (TJs) are multi-protein complexes which are crucial for the integrity and function of the epithelial barrier as they not only link cells but also form channels allowing permeation between cells, resulting in epithelial surfaces of different tightness. Tight junction’s molecular composition, ultrastructure, and function are regulated differently with regard to physiological and pathological stimuli. Both in vivo and in vitro studies suggest that reduced tight junction integrity greatly results in a condition commonly known as “leaky gut”. A loss of barrier integrity allows the translocation of luminal antigens (microbes, toxins) via the mucosa to access the whole body which are normally excluded and subsequently destroys the gut mucosal homeostasis, coinciding with an increased susceptibility to systemic infection, chronic inflammation and malabsorption. There is considerable evidence that the intestinal barrier dysfunction is an important factor contributing to the pathogenicity of some enteric bacteria. It has been shown that some enteric pathogens can induce permeability defects in gut epithelia by altering tight junction proteins, mediated by their toxins. Resolving the strategies that microorganisms use to hijack the functions of tight junctions is important for our understanding of microbial pathogenesis, because some pathogens can utilize tight junction proteins as receptors for attachment and subsequent internalization, while others modify or destroy the tight junction proteins by different pathways and thereby provide a gateway to the underlying tissue. This review aims to deliver an overview of the tight junction structures and function, and its role in enteric bacterial pathogenesis with a special focus on chickens. A main conclusion will be that the molecular mechanisms used by enteric pathogens to disrupt epithelial barrier function in chickens needs a much better understanding, explicitly highlighted for Campylobacter jejuni, Salmonella enterica and Clostridium perfringens. This is a requirement in order to assist in discovering new strategies to avoid damages of the intestinal barrier or to minimize consequences from infections.