艾滋病毒感染与免疫激活：合并感染的作用
HIV infection and immune activation: the role of coinfections.
作者信息
Boulougoura Afroditi, Sereti Irini
机构信息
HIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
出版信息
Curr Opin HIV AIDS. 2016 Mar;11(2):191-200. doi: 10.1097/COH.0000000000000241.
PURPOSE OF REVIEW
This article explores new data from recent studies addressing the role of coinfections in immune activation in HIV-1-infected patients, with a focus on immune reconstitution inflammatory syndrome (IRIS), an aberrant inflammatory response occurring shortly after antiretroviral therapy (ART) initiation.
RECENT FINDINGS
Chronic HIV infection is associated with several coinfections that contribute to immune activation in various settings including early after ART initiation in the most noticeable form of IRIS and also in chronic-treated infection, with chronic viral infections like cytomegalovirus and hepatitis C or hepatitis B virus contributing to immune activation and also morbidity and mortality. Expanding on older studies, the role of T cells in IRIS has been further elucidated with evidence of more pronounced effector activity in patients with IRIS that may be leading to excessive tissue disorder. Newer studies are also continuing to shed light on the role of myeloid cells as well as the contribution of antigen load in IRIS. In addition, preliminary data are beginning to suggest a possible role of inflammasome formation in IRIS. In cryptococcal IRIS, the role of activated immune cells (T cell and myeloid) and biomarkers were evaluated in more detail at the site of infection (cerebrospinal fluid). Finally, important differences of patients developing IRIS versus those who die from tuberculosis despite ART initiation were reported, a distinction that may have important implications for participant selection in studies aiming to prevent IRIS with immunosuppressive agents.
SUMMARY
Better understanding of the role of opportunistic infections at ART initiation and IRIS pathogenesis will assist in improved strategies for prevention and treatment. The long-term consequences of IRIS remain unclear. Chronic viral coinfections with herpesviruses and hepatitis C virus are important factors in persistent immune activation in chronic-treated HIV.
综述目的
本文探讨了近期研究中的新数据，这些研究涉及合并感染在HIV-1感染患者免疫激活中的作用，重点关注免疫重建炎症综合征（IRIS），这是一种在开始抗逆转录病毒治疗（ART）后不久发生的异常炎症反应。
最新发现
慢性HIV感染与多种合并感染相关，这些合并感染在各种情况下都会导致免疫激活，包括在ART开始后早期以最明显的IRIS形式出现，以及在长期接受治疗的感染中，如巨细胞病毒、丙型肝炎或乙型肝炎病毒等慢性病毒感染会导致免疫激活以及发病和死亡。在早期研究的基础上，T细胞在IRIS中的作用得到了进一步阐明，有证据表明IRIS患者的效应器活性更为明显，这可能导致过度的组织紊乱。新的研究也在继续揭示髓样细胞的作用以及抗原负荷在IRIS中的作用。此外，初步数据开始表明炎性小体形成在IRIS中可能发挥作用。在隐球菌性IRIS中，在感染部位（脑脊液）更详细地评估了活化免疫细胞（T细胞和髓样细胞）的作用及生物标志物。最后，报告了发生IRIS的患者与尽管开始ART但仍死于结核病的患者之间的重要差异，这一差异可能对旨在用免疫抑制剂预防IRIS的研究中的参与者选择具有重要意义。
总结
更好地了解ART开始时机会性感染的作用以及IRIS发病机制将有助于改进预防和治疗策略。IRIS的长期后果仍不清楚。与疱疹病毒和丙型肝炎病毒的慢性病毒合并感染是慢性治疗的HIV患者持续免疫激活的重要因素。
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