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爱尔兰抗-D 队列中丙型肝炎病毒耐药女性的 TLR3 反应增强。

Enhanced TLR3 responsiveness in hepatitis C virus resistant women from the Irish anti-D cohort.

机构信息

School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.

Translational Immunology Unit, Institut Pasteur, Paris, France.

出版信息

Cell Rep Med. 2022 Nov 15;3(11):100804. doi: 10.1016/j.xcrm.2022.100804. Epub 2022 Nov 4.

DOI:10.1016/j.xcrm.2022.100804
PMID:36334594
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9729829/
Abstract

Natural resistance to infection is an overlooked outcome after hepatitis C virus (HCV) exposure. Between 1977 and 1979, 1,200 Rhesus D-negative Irish women were exposed to HCV-contaminated anti-D immunoglobulin. Here, we investigate why some individuals appear to resist infection despite exposure (exposed seronegative [ESN]). We screen HCV-resistant and -susceptible donors for anti-HCV adaptive immune responses using ELISpots and VirScan to profile antibodies against all know human viruses. We perform standardized ex vivo whole blood stimulation (TruCulture) assays with antiviral ligands and assess antiviral responses using NanoString transcriptomics and Luminex proteomics. We describe an enhanced TLR3-type I interferon response in ESNs compared with seropositive women. We also identify increased inflammatory cytokine production in response to polyIC in ESNs compared with seropositive women. These enhanced responses may have contributed to innate immune protection against HCV infection in our cohort.

摘要

天然抗感染能力是丙型肝炎病毒 (HCV) 暴露后的一个被忽视的结果。1977 年至 1979 年间，1200 名 RhD 阴性爱尔兰妇女接触了含有 HCV 的抗-D 免疫球蛋白。在这里，我们研究了为什么一些人尽管暴露（暴露后血清阴性 [ESN]）但似乎仍能抵抗感染。我们使用 ELISpots 和 VirScan 对 HCV 抗性和敏感性供体进行抗 HCV 适应性免疫反应筛查，以针对所有已知的人类病毒对抗体进行分析。我们用抗病毒配体进行标准化的体外全血刺激（TruCulture）测定，并使用 NanoString 转录组学和 Luminex 蛋白质组学评估抗病毒反应。与血清阳性女性相比，我们描述了 ESN 中增强的 TLR3-Ⅰ型干扰素反应。与血清阳性女性相比，我们还发现 ESN 对 polyIC 的炎症细胞因子产生增加。这些增强的反应可能有助于我们队列中针对 HCV 感染的先天免疫保护。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/9729829/fa2cced2f989/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/9729829/e765bff76ad4/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/9729829/98facd823038/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/9729829/085b0941d00e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/9729829/adfd2a86154d/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/9729829/5e84174741bc/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/9729829/3a6a431fb29e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/9729829/ae3bddf889e0/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/9729829/fa2cced2f989/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/9729829/e765bff76ad4/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/9729829/98facd823038/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/9729829/085b0941d00e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/9729829/adfd2a86154d/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/9729829/5e84174741bc/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/9729829/3a6a431fb29e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/9729829/ae3bddf889e0/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/9729829/fa2cced2f989/gr7.jpg

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