HIV与衰老:HIV被视为一种慢性炎症性肠道疾病。

M. Gnoni
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摘要

在引入成功的抗逆转录病毒疗法(ART)后,艾滋病毒已成为一种慢性感染,生存率显著提高。然而,即使是被认为“得到最佳治疗”的艾滋病毒感染者,其非艾滋病定义疾病(心血管、呼吸系统、神经系统、代谢、肾脏和肝脏疾病)以及不同类型的实体和血液恶性肿瘤的患病率也很高,这导致了由于持续炎症和免疫激活“炎症”而导致“加速衰老”的概念。这篇综述强调了功能失调的胃肠道粘膜在系统性炎症发生中的重要性,并为未来可能的临床试验提供了见解,以达到与ART一起的功能性治愈。微生物易位、Th17和MAIT细胞、免疫细胞的“warburg样”免疫表型转换、吲哚胺2,3-双加氧酶(IDO-1)活性、微生物组的改变(生态失调)和短链脂肪酸(SCFAs)的核心作用都是这种炎症模型的重要组成部分。未来的研究将集中在胃肠道粘膜水平的紧密连接改变上,这对于制定策略以达到功能性治愈是至关重要的。
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HIV and Aging: HIV seen as a Chronic Inflammatory Intestinal Disease.
After the introduction of successful antiretroviral therapy (ART) HIV has become a chronic infection with significantly increased survival. However, even HIV-infected patients who are considered “optimally treated” have a high prevalence of non-AIDS defining illnesses (cardiovascular, respiratory, neurologic, metabolic, renal, and liver disease) along with different types of solid and hematologic malignancies which led to the concept of “Accelerated aging” due to persistent inflammation and immune-activation “Inflammaging”. This review emphasizes the importance of the dysfunctional GI mucosa on the genesis of systemic inflammation and provides insights about possible future clinical trials to reach a functional cure along with ART. Microbial translocation, the Th17 and MAIT cells, the “Warburg-like” immunophenotype switch of immune cells, the indoleamine 2,3-dioxygenase (IDO-1) activity, the alteration of the microbiome (Dysbiosis), and the central role of Short Chain Fatty Acids (SCFAs) are all important parts of this model of inflammaging. Future studies focused on the tight junction alterations at the GI mucosa level will be essential to develop strategies in order to reach a functional cure.
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