Interaction of Streptococcus agalactiae and Cellular Innate Immunity in Colonization and Disease.
Interaction of Streptococcus agalactiae and Cellular Innate Immunity in Colonization and Disease.
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DOI：
10.3389/fimmu.2014.00519
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发表时间：
2014
影响因子：
7.3
通讯作者：
Henneke P
中科院分区：
文献类型：
--
作者：
Landwehr-Kenzel S;Henneke P
无乳链球菌（B 族链球菌，GBS）高度适应人类，是肠道和阴道菌群的正常组成部分。然而，GBS 具有高度侵袭性，会导致老年人和糖尿病患者在生命之初出现过度炎症、败血症和死亡。因此，GBS是一种在健康宿主中繁衍生息的模型致病生物，但在与人类共同进化过程中并没有失去其潜在的毒力。目前尚不完全了解先天免疫系统如何在自然生态位、肠道和生殖道中含有 GBS，以及哪些分子事件导致皮肤粘膜抵抗力崩溃。出生后第 7 天至第 90 天的新生儿面临着特别引人注目的败血症表现（迟发性疾病）的风险，其中从定植到入侵和传播的转变，以及从健康到严重败血症的转变通常是暴发性的且不可预测。绝大多数迟发性脓毒症病例是由一种克隆 GBS ST17 引起的，该克隆表达 HvgA 作为标志性毒力因子和粘附素。在小鼠中，HvgA 促进穿过粘膜屏障和血脑屏障。 HvgA 和其他 GBS 毒力因子（例如菌毛和毒素）的表达水平受到上游双组分控制系统 CovR/S 的调节。这反过来又受到酸性上皮 pH 值、高葡萄糖水平以及通过小鼠肠道的过程的调节。入侵后，GBS 能够通过甘油醛-3-磷酸脱氢酶依赖性诱导 IL-10 和 β-蛋白与抑制性吞噬细胞受体唾液酸结合免疫球蛋白样凝集素 5 和 14 结合等机制破坏先天免疫。在宿主方面，Toll 样受体和炎症小体对 GBS 核酸和脂肽的感知似乎对于宿主抵抗 GBS 至关重要。然而，关于 GBS 和人类免疫细胞在定植位点之间相互作用的综合模型才刚刚出现。
Streptococcus agalactiae (Group B streptococcus, GBS) is highly adapted to humans, where it is a normal constituent of the intestinal and vaginal flora. Yet, GBS has highly invasive potential and causes excessive inflammation, sepsis, and death at the beginning of life, in the elderly and in diabetic patients. Thus, GBS is a model pathobiont that thrives in the healthy host, but has not lost its potential virulence during coevolution with mankind. It remains incompletely understood how the innate immune system contains GBS in the natural niches, the intestinal and genital tracts, and which molecular events underlie breakdown of mucocutaneous resistance. Newborn infants between days 7 and 90 of life are at risk of a particularly striking sepsis manifestation (late-onset disease), where the transition from colonization to invasion and dissemination, and thus from health to severe sepsis is typically fulminant and not predictable. The great majority of late-onset sepsis cases are caused by one clone, GBS ST17, which expresses HvgA as a signature virulence factor and adhesin. In mice, HvgA promotes the crossing of both the mucosal and the blood–brain barrier. Expression levels of HvgA and other GBS virulence factors, such as pili and toxins, are regulated by the upstream two-component control system CovR/S. This in turn is modulated by acidic epithelial pH, high glucose levels, and during the passage through the mouse intestine. After invasion, GBS has the ability to subvert innate immunity by mechanisms like glycerinaldehyde-3-phosphate-dehydrogenase-dependent induction of IL-10 and β-protein binding to the inhibitory phagocyte receptors sialic acid binding immunoglobulin-like lectin 5 and 14. On the host side, sensing of GBS nucleic acids and lipopeptides by both Toll-like receptors and the inflammasome appears to be critical for host resistance against GBS. Yet, comprehensive models on the interplay between GBS and human immune cells at the colonizing site are just emerging.