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首页> 外文期刊>Journal of Infectious Diseases >Severe Tuberculosis Induces Unbalanced Up-Regulation of Gene Networks and Overexpression of IL-22, MIP-1α, CCL27, IP-10, CCR4, CCR5, CXCR3, PD1, PDL2, IL-3, IFN-β, TIM1, and TLR2 but Low Antigen-Specific Cellular Responses
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Severe Tuberculosis Induces Unbalanced Up-Regulation of Gene Networks and Overexpression of IL-22, MIP-1α, CCL27, IP-10, CCR4, CCR5, CXCR3, PD1, PDL2, IL-3, IFN-β, TIM1, and TLR2 but Low Antigen-Specific Cellular Responses

机译:严重结核病导致基因网络的不平衡上调和IL-22,MIP-1α,CCL27,IP-10,CCR4,CCR5,CXCR3,PD1,PDL2,IL-3,IFN-β,TIM1和TLR2的过度表达,但低抗原特异性细胞反应

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摘要

The immune mechanisms by which early host-mycobacterium interaction leads to the development of severe tuberculosis (TB) remain poorly characterized in humans. Here, we demonstrate that severe TB in juvenile rhesus monkeys down-regulated many genes in the blood but up-regulated selected genes constituting gene networks of Th17 and Th1 responses, T cell activation and migration, and inflammation and chemoattractants in the pulmonary and lymphoid compartments. Overexpression (450–2740-fold) of 13 genes encoding inflammatory cytokines and receptors (IL-22, CCL27, MIP-1α, IP-10, CCR4, CCR5, and CXCR3), immune dysfunctional receptors and ligands (PD1 and PDL2), and immune activation elements (IL-3, IFN-β, TIM1, and TLR2) was seen in tissues, with low antigen-specific cellular responses. Thus, severe TB in macaques features unbalanced up-regulation of immune-gene networks without proportional increases in antigen-specific cellular responses.
机译:早期宿主-分枝杆菌相互作用导致严重结核病(TB)发生的免疫机制在人类中尚不明确。在这里,我们证明了幼年猕猴中的严重结核病下调了血液中的许多基因,但上调了构成Th17和Th1反应,T细胞活化和迁移,肺和淋巴区室的炎症和化学引诱剂的基因网络的选定基因。编码炎症性细胞因子和受体(IL-22,CCL27,MIP-1α,IP-10,CCR4,CCR5和CXCR3)的13个基因,免疫功能异常的受体和配体(PD1和PDL2)的过表达(450-2740倍),在组织中发现免疫激活元件(IL-3,IFN-β,TIM1和TLR2)具有低抗原特异性细胞应答。因此,猕猴中严重的TB具有免疫基因网络上调不平衡的特点,而抗原特异性细胞反应却没有成比例的增加。

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