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

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


    Biomed Res


    . 2021;42(2):53-66.
    doi: 10.2220/biomedres.42.53.
    Dectin-2-mediated initiation of immune responses caused by influenza virus hemagglutinin


    Hideki Yamamoto 1 , Chikako Tomiyama 2 , Ko Sato 3 , Jun Kasamatsu 3 , Kazuki Takano 4 , Aya Umeki 4 , Nana Nakahata 4 , Tomomitsu Miyasaka 5 , Emi Kanno 6 , Hiromasa Tanno 6 , Sho Yamasaki 7 , Shinobu Saijo 8 , Yoichiro Iwakura 9 , Keiko Ishii 4 , Kazuyoshi Kawakami 3 4



    AffiliationsFree article

    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-?-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.


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