Th17, gut, and HIV: therapeutic implications.
Th17, gut, and HIV: therapeutic implications.
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DOI：
10.1097/coh.0b013e32833647d9
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发表时间：
2010-03
影响因子：
4.1
通讯作者：
Hunt PW
中科院分区：
文献类型：
--
作者：
Hunt PW
本综述的目的是讨论持续免疫激活和炎症对 HIV 感染者治疗的发病率和死亡率的明显影响，探讨 Th17 T 细胞耗竭在此过程中的潜在作用，并讨论潜在的治疗意义。虽然绝大多数艾滋病毒感染者现在可以通过现代抗逆转录病毒疗法（ART）实现并维持病毒抑制，但他们的预期寿命仍然比普通人群短得多，而且他们患上通常与衰老相关的非艾滋病相关疾病（非艾滋病相关癌症、心血管疾病等）的风险仍然要高得多。尽管持续抑制病毒，但异常水平的免疫激活和炎症仍然存在，并可能导致这些临床事件。虽然持续免疫激活的原因尚未完全确定，但肠道相关淋巴组织 (GALT) 中潜伏感染细胞持续低水平的 HIV 复制和/或释放以及微生物易位可能发挥了重要作用。 ART 期间未能恢复 GALT 中的 Th17 细胞可能会损害肠粘膜屏障的恢复和微生物产物的清除。最近发病机制研究的见解可能会提出旨在恢复 GALT 中 Th17 细胞的新治疗方法，从而减少治疗 HIV 感染期间的微生物易位、免疫激活以及最终的发病率和死亡率。
The purpose of this review is to discuss the apparent impact of persistent immune activation and inflammation on morbidity and mortality among treated HIV-infected individuals, to explore the potential role of Th17 T cell depletion in this process, and to discuss potential therapeutic implications. While the vast majority of HIV-infected individuals can now achieve and maintain viral suppression with modern antiretroviral therapy (ART), their life expectancy remains much shorter than the general population and they continue to be at much higher risk for non-AIDS-associated diseases commonly associated with aging (non-AIDS-associated cancer, cardiovascular disease, etc). Abnormal levels of immune activation and inflammation persist despite sustained viral suppression and may drive these clinical events. While the causes of persistent immune activation remain incompletely characterized, persistent low-level HIV replication and/or release from latently infected cells in gut-associated lymphoid tissue (GALT) and microbial translocation likely play a major role. Failure to restore Th17 cells in GALT during ART might impair both the recovery of the gut mucosal barrier and the clearance of microbial products. Insights from recent pathogenesis studies might suggest novel therapeutic approaches designed to restore Th17 cells in GALT, thereby decreasing microbial translocation, immune activation, and ultimately morbidity and mortality during treated HIV infection.