Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA, USA.
Gut Microbes. 2012 Mar-Apr;3(2):62-70. doi: 10.4161/gmic.19141. Epub 2012 Mar 1.
The innate immune system provides the first line of defense against invading microorganisms by inducing a variety of inflammatory and antimicrobial responses. These responses are particularly important in the gastrointestinal tract, where the needs for efficient nutrient uptake and host defense collide. Many pathogens have evolved to specifically colonize the intestine, causing millions of cases of enteric infections a year. A paradigm of an enteric pathogen is Salmonella enterica, a gram-negative bacterium that causes a wide range of gastrointestinal and systemic diseases. Infections with Salmonella enterica serovar Typhimurium (S. typhimurium) lead to an acute intestinal inflammation in human and animal hosts, as a result of the bacterium invading the mucosa. A distinctive feature of Salmonella is that it has not only adapted to survive in a strong inflammatory environment, but it also uses this adaptation as a strategy to gain a growth advantage over the intestinal microbiota. We will use the model organism S. typhimurium to discuss the innate immune mechanisms employed by the mammalian gastrointestinal system and how the pathogen responds and subverts these mechanisms. In particular, we focus on the recognition of extra- and intra-cellular Salmonellae by germline-encoded pattern recognition receptors of the TLR and NLR families, and how Salmonella might profit from the activation of these receptors.
先天免疫系统通过诱导多种炎症和抗菌反应，为抵御入侵的微生物提供了第一道防线。这些反应在胃肠道中尤为重要，因为在胃肠道中，需要高效地吸收营养和进行宿主防御。许多病原体已经进化到专门在肠道中定殖，导致每年有数百万人患上肠道感染。肠道病原体的一个范例是沙门氏菌（Salmonella enterica），这是一种革兰氏阴性细菌，可引起广泛的胃肠道和全身疾病。感染鼠伤寒沙门氏菌（Salmonella enterica serovar Typhimurium，S. typhimurium）会导致人类和动物宿主发生急性肠道炎症，这是由于细菌侵入了黏膜。沙门氏菌的一个显著特点是，它不仅适应了在强烈的炎症环境中生存，而且还利用这种适应作为一种策略，从肠道微生物群中获得生长优势。我们将使用模式生物鼠伤寒沙门氏菌来讨论哺乳动物胃肠道系统所采用的先天免疫机制，以及病原体如何应对和颠覆这些机制。特别是，我们将重点关注 TLR 和 NLR 家族中胚系编码的模式识别受体对细胞外和细胞内沙门氏菌的识别，以及沙门氏菌如何从这些受体的激活中获益。
