Viruses, Aging, and Chronic Lung Disease.
Viruses, Aging, and Chronic Lung Disease.
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病毒、衰老和慢性肺病。
DOI：
10.1164/rccm.201802-0234ed
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发表时间：
2018
影响因子：
24.7
通讯作者：
Twigg3rd,HomerL
中科院分区：
文献类型：
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作者：
Twigg3rd,HomerL
抗逆转录病毒时代预示着艾滋病毒感染人群中公认的肺部并发症发生了重大转变。肺部感染已被慢性肺部疾病（包括慢性阻塞性肺疾病、癌症和肺动脉高压）患病率增加所取代（1）。这种改善大部分归因于控制系统性病毒血症带来的免疫重建。因此，HIV感染患者现在的寿命几乎正常（2）。然而，在本期《日刊》中，我们要提醒大家，尽管在艾滋病毒感染的管理方面取得了医学上的成功，但肺部疾病仍然是这一人群发病的一个重要原因。在一项仔细进行的研究中，Collini和他的同事（pp. 1604-1615）检测了HIV感染对巨噬细胞胞内杀伤肺炎球菌的影响（3）。他们首先证明，在体外用HIV感染单核细胞衍生的巨噬细胞，通过巨噬细胞介导的细胞凋亡导致摄入的肺炎球菌的晚期杀伤显著降低，而不改变初始肺炎球菌摄取和吞噬溶酶体杀伤。这是通过降低肺炎球菌下调HIV感染细胞中抗凋亡蛋白Mcl-1的能力介导的，这导致caspase 3/7表达降低。第二，所有这些发现都在接受抗逆转录病毒治疗（ART）的HIV感染者的肺泡巨噬细胞中重现。第三，研究人员证明了病毒蛋白在许多ART患者的肺部中的持续存在，并且单核细胞衍生的巨噬细胞单独暴露于gp 120导致暴露于全病毒后在巨噬细胞中观察到的所有肺炎球菌吞噬和凋亡缺陷。最后，HIV感染者和健康志愿者的肺泡巨噬细胞的转录活性比较显示没有显著差异，尽管后者的结果受到这些实验中研究的受试者数量少的限制（HIV，n= 8;健康，n= 5）。首先，在他们的研究中，ART的中位时间是75个月。人们会认为这是足够的时间来确保充分的免疫重建，特别是考虑到肺病毒控制和BAL细胞CD 4计数的改善最快可在6个月内观察到
The antiretroviral era has heralded a significant shift in lung complications recognized in the HIV-infected population. Opportunistic infections have been replaced by an increased prevalence of chronic lung diseases, including chronic obstructive lung disease, cancer, and pulmonary hypertension (1). Much of this improvement has been attributed to the immune reconstitution that comes with control of systemic viremia. As a result, patients with HIV infection now have nearly normal life spans (2). However, in this issue of the Journal, we are reminded that despite medical successes in the management of HIV infection, lung disease continues to be a significant cause of morbidity in this population. In a carefully performed study, Collini and colleagues (pp. 1604–1615) examined the effect of HIV infection on intracellular killing of pneumococci by macrophages (3). They first demonstrated that infecting monocyte-derived macrophages with HIV in vitro resulted in significantly lower late killing of ingested pneumococci through mitochondria-mediated cell apoptosis, without altering initial pneumococci uptake and phagolysosomal killing. This was mediated through a decreased ability of pneumococci to downregulate the antiapoptotic protein Mcl-1 in HIV-infected cells, which resulted in decreased caspase 3/7 expression. Second, all of these findings were recapitulated in alveolar macrophages from HIV-infected subjects on antiretroviral therapy (ART). Third, the investigators demonstrated the persistence of viral proteins in the lungs of many patients on ART, and that exposure of monocyte-derived macrophages to gp120 alone resulted in all of the pneumococcal phagocytic and apoptotic defects seen in macrophages after exposure to whole virus. Finally, a comparison of transcriptional activity in alveolar macrophages from HIV-infected subjects and healthy volunteers showed no significant differences, although the latter result is limited significantly by the low number of subjects studied in these experiments (HIV, n= 8; healthy, n= 5).The findings from this study are sobering on several fronts. First, the median time on ART in their study was 75 months. One would think that this is more than enough time to ensure adequate immune reconstitution, especially considering that pulmonary viral control and improvements in BAL cell CD4 counts can be seen as soon as 6 months