Transcriptional Immunoprofiling at the Tick-Virus-Host Interface during Early Stages of Tick-Borne Encephalitis Virus Transmission.

Transcriptional Immunoprofiling at the Tick-Virus-Host Interface during Early Stages of Tick-Borne Encephalitis Virus Transmission.
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DOI:
10.3389/fcimb.2017.00494
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发表时间:
2017
影响因子:
5.7
通讯作者:
Kazimirova M
Kazimirova M
中科院分区:
医学2区
文献类型:
--
作者:
Thangamani S;Hermance ME;Santos RI;Slovak M;Heinze D;Widen SG;Kazimirova M

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由吸血节肢动物传播的新出现和重新出现的疾病是重大的全球公共卫生问题。在所有吸血节肢动物中,蜱传播的病原微生物种类最多。由蜱传播的传染性病原体与叮咬部位的唾液一起传递给脊椎动物宿主。蜱的唾液腺产生复杂的生物活性分子混合物,通过调节宿主止血、疼痛/瘙痒反应、伤口愈合以及先天性和适应性免疫来促进血液喂养和病原体传播。在这项研究中,我们利用 Illumina 新一代测序技术来表征皮肤免疫反应对蓖麻硬蜱传播的蜱传脑炎病毒 (TBEV) 的转录免疫谱。对感染 TBEV 和未感染的蜱进食地点进行了比较免疫基因表达分析。我们的分析表明,蜱虫在进食的前 3 小时内会在叮咬部位产生炎症环境,并且在感染 TBEV 的蜱虫和未感染的蜱虫进食之间观察到宿主反应的显着差异。基因表达分析揭示了感染 TBEV 的蜱饲喂 1 小时和 3 小时后炎症基因的调节。趋化因子和细胞因子特异性基因的转录水平表明中性粒细胞主导的免疫反应。蜱取食部位的免疫组织化学显示,单核吞噬细胞和成纤维细胞是TBEV感染的主要靶细胞,并且在中性粒细胞中未检测到TBEV抗原。总之,转录和免疫组织化学结果表明,早期皮肤宿主对 TBEV 感染的蜱喂养的反应比预期更具炎症性,并强调了炎症趋化因子和细胞因子途径在蜱传黄病毒传播中的重要性。
Emerging and re-emerging diseases transmitted by blood feeding arthropods are significant global public health problems. Ticks transmit the greatest variety of pathogenic microorganisms of any blood feeding arthropod. Infectious agents transmitted by ticks are delivered to the vertebrate host together with saliva at the bite site. Tick salivary glands produce complex cocktails of bioactive molecules that facilitate blood feeding and pathogen transmission by modulating host hemostasis, pain/itch responses, wound healing, and both innate and adaptive immunity. In this study, we utilized Illumina Next Generation Sequencing to characterize the transcriptional immunoprofile of cutaneous immune responses to Ixodes ricinus transmitted tick-borne encephalitis virus (TBEV). A comparative immune gene expression analysis of TBEV-infected and uninfected tick feeding sites was performed. Our analysis reveals that ticks create an inflammatory environment at the bite site during the first 3 h of feeding, and significant differences in host responses were observed between TBEV-infected and uninfected tick feeding. Gene-expression analysis reveals modulation of inflammatory genes after 1 and 3 h of TBEV-infected tick feeding. Transcriptional levels of genes specific to chemokines and cytokines indicated a neutrophil-dominated immune response. Immunohistochemistry of the tick feeding site revealed that mononuclear phagocytes and fibroblasts are the primary target cells for TBEV infection and did not detect TBEV antigens in neutrophils. Together, the transcriptional and immunohistochemistry results suggest that early cutaneous host responses to TBEV-infected tick feeding are more inflammatory than expected and highlight the importance of inflammatory chemokine and cytokine pathways in tick-borne flavivirus transmission.
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发表时间: 1996-12-01
影响因子: 2.2
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