TLR刺激后天然细胞产生白细胞介素1-β（IL-1β）与接受抗逆转录病毒治疗的HIV感染患者的结核病复发相关。

Interleukin 1-Beta (IL-1β) Production by Innate Cells Following TLR Stimulation Correlates With TB Recurrence in ART-Treated HIV-Infected Patients.

作者信息

Thobakgale Christina, Naidoo Kewreshini, McKinnon Lyle R, Werner Lise, Samsunder Natasha, Karim Salim Abdool, Ndungʼu Thumbi, Altfeld Marcus, Naidoo Kogieleum

机构信息

*HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; †Centre for the AIDS Programme of Research in South Africa, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; ‡Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA; §MRC HIV-TB Pathogenesis and Treatment Research Unit, CAPRISA; ‖Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada; ¶KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; #Max Planck Institute for Infection Biology, Berlin, Germany; and **Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.

出版信息

J Acquir Immune Defic Syndr. 2017 Feb 1;74(2):213-220. doi: 10.1097/QAI.0000000000001181.

DOI:10.1097/QAI.0000000000001181

PMID:27654812

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5237660/

Abstract

BACKGROUND

Tuberculosis (TB) remains a major cause of global morbidity and mortality, especially in the context of HIV coinfection because immunity is not completely restored following antiretroviral therapy (ART). The identification of immune correlates of risk for TB disease could help in the design of host-directed therapies and clinical management. This study aimed to identify innate immune correlates of TB recurrence in HIV+ ART-treated individuals with a history of previous successful TB treatment.

METHODS

Twelve participants with a recurrent episode of TB (cases) were matched for age, sex, time on ART, pre-ART CD4 count with 12 participants who did not develop recurrent TB in 60 months of follow-up (controls). Cryopreserved peripheral blood mononuclear cells from time-points before TB recurrence were stimulated with ligands for Toll-like receptors (TLR) including TLR-2, TLR-4, and TLR-7/8. Multicolor flow cytometry and intracellular cytokine staining were used to detect IL-1β, TNF-α, IL-12, and IP10 responses from monocytes and myeloid dendritic cells (mDCs).

RESULTS

Elevated production of IL-1β from monocytes following TLR-2, TLR-4, and TLR-7/8 stimulation was associated with reduced odds of TB recurrence. In contrast, production of IL-1β from both monocytes and mDCs following Bacillus Calmette-Guérin (BCG) stimulation was associated with increased odds of TB recurrence (risk of recurrence increased by 30% in monocytes and 42% in mDCs, respectively).

CONCLUSION

Production of IL-1β by innate immune cells following TLR and BCG stimulations correlated with differential TB recurrence outcomes in ART-treated patients and highlights differences in host response to TB.

摘要

背景

结核病仍然是全球发病和死亡的主要原因，尤其是在合并感染艾滋病毒的情况下，因为抗逆转录病毒疗法（ART）后免疫功能不能完全恢复。确定结核病发病风险的免疫相关因素有助于宿主导向疗法的设计和临床管理。本研究旨在确定既往有成功结核病治疗史的HIV阳性且接受ART治疗的个体中结核病复发的固有免疫相关因素。

方法

12名有结核病复发的参与者（病例组）在年龄、性别、接受ART的时间、ART前CD4细胞计数方面与12名在60个月随访中未发生结核病复发的参与者（对照组）进行匹配。用Toll样受体（TLR）配体刺激结核病复发前时间点冻存的外周血单个核细胞，这些配体包括TLR-2、TLR-4和TLR-7/8。采用多色流式细胞术和细胞内细胞因子染色检测单核细胞和髓样树突状细胞（mDC）产生的IL-1β、TNF-α、IL-12和IP10反应。