人类扁桃体的单细胞转录组学揭示尼古丁能增强 HIV-1 诱导的 NLRP3 炎症小体和线粒体活化。

IF 3.8 3区 医学 Q2 VIROLOGY
Viruses-Basel Pub Date : 2024-11-20 DOI:10.3390/v16111797
Nadine Schrode, Trinisia Fortune, Aislinn M Keane, Jesse F Mangold, Benjamin Tweel, Kristin G Beaumont, Talia H Swartz
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引用次数: 0

摘要

背景:即使接受了有效的抗逆转录病毒疗法(ART),HIV-1 感染仍与慢性炎症和免疫功能障碍有关,从而导致长期的健康并发症。在艾滋病病毒感染者(PWH)中普遍使用尼古丁,已知会加剧免疫活化和疾病进展,但其确切的生物学机制仍有待充分了解。本研究试图揭示 HIV-1 感染和尼古丁对免疫细胞功能的协同作用,重点是对 NLRP3 炎症小体激活、氧化应激和线粒体途径的有益认识。方法:用人类扁桃体外植体感染 HIV-1 并接触尼古丁,利用单细胞 RNA 测序分析免疫细胞群以及与炎性体活化、氧化应激和线粒体功能相关的基因表达。研究人员还进行了基因组富集分析(GSEA)和协同作用评估,以研究尼古丁如何在艾滋病病毒感染的情况下调节免疫反应:结果:HIV 感染和尼古丁暴露的结合会显著增加 NLRP3 炎症小体的激活、硫氧还蛋白和氧化磷酸化成分:这项研究强调了HIV-1和尼古丁的共同作用如何为免疫调节提供了宝贵的见解,为未来的治疗策略打开了大门。针对 NLRP3 炎性体和尼古丁的使用可能有助于改善 PWH 的治疗效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Single-Cell Transcriptomics of Human Tonsils Reveals Nicotine Enhances HIV-1-Induced NLRP3 Inflammasome and Mitochondrial Activation.

Background: HIV-1 infection, even with effective antiretroviral therapy (ART), is associated with chronic inflammation and immune dysfunction, contributing to long-term health complications. Nicotine use, prevalent among people with HIV (PWH), is known to exacerbate immune activation and disease progression, but the precise biological mechanisms remain to be fully understood. This study sought to uncover the synergistic effects of HIV-1 infection and nicotine on immune cell function, focusing on beneficial insights into NLRP3 inflammasome activation, oxidative stress, and mitochondrial pathways.

Methods: Human tonsil explants were infected with HIV-1 and exposed to nicotine. Single-cell RNA sequencing was used to profile immune cell populations and gene expression linked to inflammasome activation, oxidative stress, and mitochondrial function. Gene set enrichment analysis (GSEA) and synergy assessments were conducted to investigate how nicotine modulates immune responses in the context of HIV.

Results: The combination of HIV infection and nicotine exposure significantly increased NLRP3 inflammasome activation, thioredoxin, and components of oxidative phosphorylation.

Conclusions: This study highlights how the combined effects of HIV-1 and nicotine offer valuable insights into immune modulation, opening doors for future therapeutic strategies. Targeting the NLRP3 inflammasome and addressing nicotine use may contribute to improved outcomes for PWH.

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来源期刊
Viruses-Basel
Viruses-Basel VIROLOGY-
CiteScore
7.30
自引率
12.80%
发文量
2445
审稿时长
1 months
期刊介绍: Viruses (ISSN 1999-4915) is an open access journal which provides an advanced forum for studies of viruses. It publishes reviews, regular research papers, communications, conference reports and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. We also encourage the publication of timely reviews and commentaries on topics of interest to the virology community and feature highlights from the virology literature in the ''News and Views'' section. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.
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