Development of in vitro models to study bacterial interactions with lymphoid tissue-associated epithelial cells

健康人的鼻子和喉咙中发现了许多细菌，但脑膜炎球菌、嗜血杆菌和莫拉氏菌等一些细菌可导致严重疾病，从局部耳、喉和肺部感染到广泛的血液和脑部感染（败血症和脑膜炎）。它们可以影响年轻人和老年人。尽管可以获得一些预防由这些细菌的不同菌株引起的感染的疫苗，但是仍然需要疫苗来预防由剩余的有问题的细菌例如B群脑膜炎球菌、一些嗜血杆菌属物种和莫拉氏菌菌株引起的感染。为了确定有效的候选疫苗，我们需要确定细菌引起疾病的基本机制。几位研究人员通过使用在实验室培养物中生长的分离细胞来研究细菌如何附着和侵入喉咙衬里的人类细胞（上皮细胞）。然而，越来越多的研究表明，细菌定植的细胞，特别是喉咙扁桃体周围的细胞，与在简单的实验室培养条件下生长的细胞具有不同的特性。在这项研究中，我们建议使用复杂的培养方法来模拟上皮细胞在体内经历的环境。这些细胞模型将帮助我们更好地了解参与病原体附着和入侵的细菌和宿主成分。这样的模型系统在其他病原体的研究中也有更广泛的应用。对人体屏障渗透过程的精确机制的更完整的了解有望产生信息，使我们能够针对呼吸道病原体制定更好的治疗和其他干预/预防策略。

Many bacteria are found in the noses and throats of healthy individuals, but some bacteria such as meningococci, haemophilus and moraxella can cause serious diseases ranging from localised ear, throat and lung infections to widespread blood and brain infections (septicaemia and meningitis). They can affect both the young and the old. Although some vaccines to prevent infections caused by different strains of these bacteria are available, there is still a need for vaccines to prevent infections caused by the remaining problematic bacteria such as group B meningococci, some haemophilus species and moraxella strains. To identify effective vaccine candidates, we need to identify basic mechanisms by which bacteria cause disease. Several investigators have examined how the bacteria attach to and invade human cells lining the throat (epithelial cells) by using isolated cells grown in laboratory cultures. However, increasing numbers of studies have shown that the cells that the bacteria colonise, especially around the tonsils in the throat, possess different properties to those grown under simple laboratory culture conditions. In this study, we propose to use complex culturing methods to mimic the environment that epithelial cells experience in the body. These cellular models will help us to understand better the bacterial and host components that are involved in attachment and invasion by the pathogens. Such model systems also have a wider application for studies on other pathogens. The more complete knowledge of the precise mechanisms that underlie the processes of human barrier penetration is expected to generate information that will allow us to produce better therapeutic and other intervention / prevention strategies against respiratory tract pathogens.