A single-stranded DNA aptamer against mannose-capped lipoarabinomannan enhances anti-tuberculosis activity of macrophages through downregulation of lipid-sensing nuclear receptor peroxisome proliferator-activated receptor gamma expression
A single-stranded DNA aptamer against mannose-capped lipoarabinomannan enhances anti-tuberculosis activity of macrophages through downregulation of lipid-sensing nuclear receptor peroxisome proliferator-activated receptor gamma expression
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针对甘露糖封端的阿拉伯脂甘露聚糖的单链DNA适体通过下调脂质敏感核受体过氧化物酶体增殖物激活受体γ表达来增强巨噬细胞的抗结核活性
DOI：
10.1111/1348-0421.12470
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发表时间：
2017
影响因子：
2.6
通讯作者：
Zhang Xiao-Lian
中科院分区：
文献类型：
--
作者：
Pan Qin;Yan Jiamin;Liu Qi;Yuan Chunhui;Zhang Xiao-Lian
甘露糖帽脂阿拉伯甘露聚糖（ManLAM）是结核分枝杆菌（Mtb）的免疫调节表位。先前产生了特异性地结合来自突变体MtbH 37 Rv菌株的ManLAM的适体（ZXL 1），并且发现ZXL 1作为拮抗剂起作用，抑制ManLAM诱导的DC的免疫抑制。在本研究中，发现ZXL 1可使小鼠巨噬细胞中的IL-1β和IL-12 mRNA表达以及ManLAM处理的巨噬细胞中的细胞因子产生增加，但IL-10产生减少。诱导型一氧化氮合酶在巨噬细胞中的表达上调ZXL 1的存在下，刺激后与ManLAM。还发现ZXL 1抑制脂质敏感核受体过氧化物酶体增殖物激活受体γ（PPAR-γ）的表达。这些结果表明，ZXL 1通过下调PPAR-γ表达促进抗结核活性，这可能有助于M1巨噬细胞极化和巨噬细胞杀伤Mtb。
Mannose‐capped lipoarabinomannan (ManLAM) is an immunomodulatory epitope ofMycobacterium tuberculosis(Mtb). An aptamer (ZXL1) that specifically binds to ManLAM from the virulentMtbH37Rv strain was previously generated and it was found that ZXL1 functions as an antagonist, inhibiting the ManLAM‐induced immunosuppression of DCs. In the present study, it was found that ZXL1 inhibitsMtbentry into murine macrophages and that ZXL1 enhances IL‐1β and IL‐12 mRNA expression and cytokine production in ManLAM‐treated macrophages but decreases IL‐10 production. Inducible nitric oxide synthase expression in macrophages was upregulated in the presence of ZXL1 after stimulation with ManLAM. ZXL1 was also found to inhibit expression of lipid‐sensing nuclear receptor peroxisome proliferator‐activated receptor γ (PPAR‐γ). These results suggest that ZXL1 promotes anti‐tuberculosis activity through downregulation of PPAR‐γ expression, which may contribute to M1 macrophage polarization andMtbkilling by macrophages.