Gut barrier structure, mucosal immunity and intestinal microbiota in the pathogenesis and treatment of HIV infection.
Gut barrier structure, mucosal immunity and intestinal microbiota in the pathogenesis and treatment of HIV infection.
复制标题
DOI：
10.1186/s12981-016-0103-1
复制
发表时间：
2016
影响因子：
2.2
通讯作者：
Marchetti G
中科院分区：
文献类型：
--
作者：
Tincati C;Douek DC;Marchetti G
在过去的10年中，在HIV感染中的微生物易位领域开展了大量的工作，从其临床意义的研究到其致病特征的调查。在目前的工作中，我们回顾了这一现象的最新发现，重点关注微生物易位在hiv相关发病率和死亡率中的预测作用，其产生的机制和潜在的治疗方法。从临床角度来看，目前的研究表明，微生物易位标记物可能有助于预测未经治疗的HIV感染的临床事件，而在经历过cart的受试者中，它们的作用存在矛盾的数据，可能是由于在队列研究中纳入了极其不同的患者群体。解决微生物易位发病机制的研究结果提高了我们对HIV感染中发生的胃肠道上皮屏障损伤的认识。然而，粘膜损伤在多大程度上直接转化为胃肠道通透性增加仍然是一个悬而未决的问题。在这方面，新的工作已经确定了IL-17和il -22分泌T细胞群在限制微生物易位和全身T细胞激活/炎症中的作用，因此代表了免疫治疗干预的可能目标，在动物模型中显示出很有希望。此外，最近的报道不仅证实了在HIV感染过程中存在一个益生菌群落，而且还表明它可能与粘膜损伤、微生物易位和外周免疫激活有关。重要的是，技术进步也揭示了肠道微生物的代谢活动，强调需要新的治疗方法来纠正胃肠道微生物群的功能和组成。
Over the past 10 years, extensive work has been carried out in the field of microbial translocation in HIV infection, ranging from studies on its clinical significance to investigations on its pathogenic features. In the present work, we review the most recent findings on this phenomenon, focusing on the predictive role of microbial translocation in HIV-related morbidity and mortality, the mechanisms by which it arises and potential therapeutic approaches. From a clinical perspective, current work has shown that markers of microbial translocation may be useful in predicting clinical events in untreated HIV infection, while conflicting data exist on their role in cART-experienced subjects, possibly due to the inclusion of extremely varied patient populations in cohort studies. Results from studies addressing the pathogenesis of microbial translocation have improved our knowledge of the damage of the gastrointestinal epithelial barrier occurring in HIV infection. However, the extent to which mucosal impairment translates directly to increased gastrointestinal permeability remains an open issue. In this respect, novel work has established a role for IL-17 and IL-22-secreting T cell populations in limiting microbial translocation and systemic T-cell activation/inflammation, thus representing a possible target of immune-therapeutic interventions shown to be promising in the animal model. Further, recent reports have not only confirmed the presence of a dysbiotic intestinal community in the course of HIV infection but have also shown that it may be linked to mucosal damage, microbial translocation and peripheral immune activation. Importantly, technical advances have also shed light on the metabolic activity of gut microbes, highlighting the need for novel therapeutic approaches to correct the function, as well as the composition, of the gastrointestinal microbiota.