Dectin-2-mediated initiation of immune responses caused by influenza virus hemagglutinin.

IF 1.3 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL
Hideki Yamamoto, Chikako Tomiyama, Ko Sato, Jun Kasamatsu, Kazuki Takano, Aya Umeki, Nana Nakahata, Tomomitsu Miyasaka, Emi Kanno, Hiromasa Tanno, Sho Yamasaki, Shinobu Saijo, Yoichiro Iwakura, Keiko Ishii, Kazuyoshi Kawakami
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引用次数: 3

Abstract

Antigen-presenting cells express pattern recognition receptors (PRRs), which sense pathogen-associated molecular patterns from microorganisms and lead to the induction of inflammatory responses. C-type lectin receptors (CLRs), the representative PRRs, bind to microbial polysaccharides, among which Dectin-2 and Mincle recognize mannose-containing polysaccharides. Because influenza virus (IFV) hemagglutinin (HA) is rich in mannose polysaccharides, Dectin-2 or Mincle may contribute to the recognition of HA. In this study, we addressed the possible involvement of Dectin-2 and Mincle in the viral recognition and the initiation of cytokine production. Interleukin (IL)-12p40 and IL-6 production by bone marrow-derived dendritic cells (BM-DCs) upon stimulation with HA was significantly reduced in Dectin-2 knockout (KO) mice compared to wild-type (WT) mice whereas there was no difference between WT mice and Mincle KO mice. BM-DCs that were treated with Syk inhibitor resulted in a significant reduction of cytokine production upon stimulation with HA. The treatment of BM-DCs with methyl-α-D-mannopyranoside (ManP) also led to a significant reduction in cytokine production by BM-DCs that were stimulated with HA, except for the A/H1N1pdm09 subtype. IL-12p40 and IL-6 synthesis by BM-DCs was completely diminished upon stimulation with HA treated with concanavalin A (ConA)-bound sepharose beads. Finally, GFP expression was detected in reporter cells that were transfected with the Dectin-2 gene, but not with the Mincle gene, when stimulated with HA derived from the A/H3N2 subtype. These data suggested that Dectin-2 may be a key molecule as the sensor for IFV to initiate the immune response and regulate the pathogenesis of IFV infection.

dectin -2介导的流感病毒血凝素引起的免疫反应的启动。
抗原呈递细胞表达模式识别受体(PRRs),其从微生物中感知病原体相关的分子模式并导致炎症反应的诱导。c型凝集素受体(C-type lecectin receptor, CLRs)与微生物多糖结合,其中Dectin-2和Mincle可识别含甘露糖的多糖。由于流感病毒(IFV)血凝素(HA)富含甘露糖多糖,Dectin-2或Mincle可能有助于HA的识别。在这项研究中,我们探讨了Dectin-2和Mincle可能参与病毒识别和细胞因子产生的启动。与野生型(WT)小鼠相比,经HA刺激的Dectin-2敲除(KO)小鼠骨髓源性树突状细胞(bm - dc)产生的白细胞介素(IL)-12p40和IL-6显著减少,而WT小鼠和Mincle KO小鼠之间没有差异。Syk抑制剂处理的bm - dc在HA刺激下导致细胞因子产生显著减少。除a /H1N1pdm09亚型外,甲基α- d -甘露吡诺苷(ManP)处理的bm - dc也导致HA刺激的bm - dc细胞因子产生显著减少。在刀豆蛋白A (ConA)结合的sepharose beads处理的HA刺激下,bmp - dc的IL-12p40和IL-6的合成完全减少。最后,用来自A/H3N2亚型的HA刺激转染Dectin-2基因而不转染Mincle基因的报告细胞,检测到GFP的表达。这些数据提示Dectin-2可能是IFV启动免疫应答和调节IFV感染发病机制的关键传感器分子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biomedical Research-tokyo
Biomedical Research-tokyo 医学-医学:研究与实验
CiteScore
2.40
自引率
0.00%
发文量
19
审稿时长
>12 weeks
期刊介绍: Biomedical Research is peer-reviewed International Research Journal . It was first launched in 1990 as a biannual English Journal and later became triannual. From 2008 it is published in Jan-Apr/ May-Aug/ Sep-Dec..
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