PDF(Pubmed)
Abstract：
Antiretroviral treatment (ART) has converted HIV from a lethal disease to a chronic condition, yet co-morbidities persist. Incomplete immune recovery and chronic immune activation, especially in the gut mucosa, contribute to these complications. Inflammasomes, multi-protein complexes activated by innate immune receptors, appear to play a role in these inflammatory responses. In particular, preliminary data indicate the involvement of IFI16 and NLRP3 inflammasomes in chronic HIV infection. This study explores inflammasome function in monocytes from people with HIV (PWH); 22 ART-treated with suppressed viremia and 17 untreated PWH were compared to 33 HIV-negative donors. Monocytes were primed with LPS and inflammasomes activated with ATP in vitro. IFI16 and NLRP3 mRNA expression were examined in a subset of donors. IFI16 and NLRP3 expression in unstimulated monocytes correlated negatively with CD4 T cell counts in untreated PWH. For IFI16, there was also a positive correlation with viral load. Monocytes from untreated PWH exhibit increased release of IL-1α, IL-1β, and TNF compared to treated PWH and HIV-negative donors. However, circulating monocytes in PWH are not pre-primed for inflammasome activation in vivo. The findings suggest a link between IFI16, NLRP3, and HIV progression, emphasizing their potential role in comorbidities such as cardiovascular disease. The study provides insights into inflammasome regulation in HIV pathogenesis and its implications for therapeutic interventions.
摘要：
抗逆转录病毒治疗（ART）已将HIV从致命疾病转变为慢性病，然而，合并症仍然存在。免疫恢复不完全和慢性免疫激活，尤其是在肠粘膜中，有助于这些并发症。炎性体,由先天免疫受体激活的多蛋白复合物，似乎在这些炎症反应中发挥作用。特别是,初步数据表明IFI16和NLRP3炎性体参与慢性HIV感染.这项研究探讨了HIV（PWH）患者单核细胞中的炎性体功能；将22例接受抑制病毒血症的ART治疗和17例未经治疗的PWH与33例HIV阴性供体进行了比较。在体外用LPS和ATP活化的炎性小体引发单核细胞。在供体的子集中检查IFI16和NLRP3mRNA表达。未刺激的单核细胞中的IFI16和NLRP3表达与未处理的PWH中的CD4T细胞计数呈负相关。对于IFI16，与病毒载量也呈正相关。来自未经处理的PWH的单核细胞显示IL-1α的释放增加，IL-1β,和TNF与治疗的PWH和HIV阴性供体相比。然而,PWH中的循环单核细胞未预先引发体内炎症小体激活。研究结果表明IFI16，NLRP3和HIV进展之间存在联系，强调它们在心血管疾病等合并症中的潜在作用。该研究提供了对HIV发病机制中炎症小体调节及其对治疗干预的影响的见解。
