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在遗传上不同的猕猴群体中,单核细胞:淋巴细胞比值与结核病进展的差异。

Differences in monocyte: lymphocyte ratio and Tuberculosis disease progression in genetically distinct populations of macaques.

机构信息

National Infection Service, Public Health England, Porton Down, Wiltshire, UK.

London School of Hygiene and Tropical Medicine, London, UK.

出版信息

Sci Rep. 2019 Mar 4;9(1):3340. doi: 10.1038/s41598-019-39819-6.

Abstract

Monocyte:lymphocyte ratio (M:L) has been identified as a risk factor in development of TB disease in children and those undergoing treatment for HIV in co-infected individuals. Retrospective analysis was performed using M:L data collected from TB modelling studies performed in Rhesus macaques of Indian genotype (RM), cynomolgus macaque of Chinese genotype (CCM) and cynomolgus macaque of Mauritian genotype (MCM), which found that the more susceptible populations (RM and MCM) had higher M:L ratios than the least susceptible population (CCM). Following Mycobacterium tuberculosis exposure, significant increases in M:L ratio were observed in susceptible RM and MCM within 12 weeks of TB infection, whereas M:L in CCM remained stable, suggesting that changes in M:L ratio may also act as a biomarker of TB disease progression. The frequency of PPD-specific interferon gamma (IFNγ) secreting cells (SFU) were compared, with the more susceptible macaque populations showing an association between M:L and IFNγ SFU frequency. Investigation of the genes associated with monocyte-derived antigen presenting cells revealed differences between RM and CCM, highlighting differences in their monocyte populations, as well as overall M:L ratio. Differences in M:L ratio between macaque populations could be used to explore immunological mechanisms in susceptible populations that would complement human population studies.

摘要

单核细胞与淋巴细胞比值(M:L)已被确定为儿童结核病发病和 HIV 感染者合并感染后发生结核病的危险因素。对来自印度恒河猴(RM)、中国食蟹猴(CCM)和毛里求斯食蟹猴(MCM)结核病建模研究中收集的 M:L 数据进行了回顾性分析,结果发现易感性更高的人群(RM 和 MCM)的 M:L 比值高于最不易感的人群(CCM)。在接触结核分枝杆菌后,易感性 RM 和 MCM 中的 M:L 比值在感染结核后 12 周内显著增加,而 CCM 中的 M:L 比值保持稳定,这表明 M:L 比值的变化也可能作为结核病进展的生物标志物。比较了 PPD 特异性干扰素γ(IFNγ)分泌细胞(SFU)的频率,易感性更高的猴群中 M:L 与 IFNγ SFU 频率之间存在相关性。对与单核细胞来源的抗原呈递细胞相关的基因进行了研究,发现 RM 和 CCM 之间存在差异,这突出了它们单核细胞群体以及整体 M:L 比值的差异。食蟹猴种群之间 M:L 比值的差异可用于探索易感人群中的免疫机制,从而补充人类种群研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76f6/6399212/3f4155989ce8/41598_2019_39819_Fig1_HTML.jpg

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