Involvement of Dectin-2 in the Innate Inflammatory Response Triggered by Influenza Virus Hemagglutinin  

作　　者：Hideki Yamamoto Chikako Tomiyama Sho Yamasaki Shinobu Saijo Yoichiro Iwakura Kazuyoshi Kawakami Hideki Yamamoto;Chikako Tomiyama;Sho Yamasaki;Shinobu Saijo;Yoichiro Iwakura;Kazuyoshi Kawakami(Department of Medical Technology, Graduate School of Health Sciences, Niigata University, Niigata, Japan;Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan;Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Osaka, Japan;Project for Cytokine Research, Division of Molecular Immunology Medical Mycology Research Center, Chiba University, Chiba, Japan;Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan;Department of Medical Microbiology, Mycology and Immunology, Tohoku University, Miyagi, Japan;Department of Internal Medicine, Hirose Hospital, Miyagi, Japan)

机构地区：[1]Department of Medical Technology, Graduate School of Health Sciences, Niigata University, Niigata, Japan [2]Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan [3]Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Osaka, Japan [4]Project for Cytokine Research, Division of Molecular Immunology Medical Mycology Research Center, Chiba University, Chiba, Japan [5]Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan [6]Department of Medical Microbiology, Mycology and Immunology, Tohoku University, Miyagi, Japan [7]Department of Internal Medicine, Hirose Hospital, Miyagi, Japan

出　　处：《Advances in Infectious Diseases》2023年第3期478-497,共20页传染病进展（英文）

摘　　要：C-type lectin receptors (CLRs) are representative pattern recognition receptors that recognize microbial polysaccharides expressed on antigen-presenting cells. In the present study, we carried out further detailed analysis on the involvement of Dectin-2, a CLR that senses high mannose polysaccharide, in innate immune responses induced by influenza virus hemagglutinin (HA). Treatment of HA with periodate or PNGase F induced lower interleukin (IL)-12p40 secretion by conventional dendritic cells (DCs) compared with the untreated group. In contrast, treatment with O-glycosidase did not affect cytokine production. Green fluorescent protein expression in canonical Dectin-2-transducing cells was approximately 3% - 12% following HA stimulation, except with the A/H1N1pdm09 subtype HA. This expression was markedly reduced in cells possessing mutated amino acids in the carbohydrate recognition domain of Dectin-2, especially following stimulation with HA derived from the A/H3N2 subtype. Interferon (IFN)-α production from CD11c⁺Siglec-H⁺PDCA-1⁺ plasmacytoid DCs was significantly increased in Dectin-2 knockout mice compared with wild-type mice upon stimulation with HA except for the B/Yamagata lineage HA. These results suggested that Dectin-2 is involved in initiating inflammatory responses via mannose polysaccharide on HA. However, other mechanisms may function in the antiviral response, including the type I IFN axis.C-type lectin receptors (CLRs) are representative pattern recognition receptors that recognize microbial polysaccharides expressed on antigen-presenting cells. In the present study, we carried out further detailed analysis on the involvement of Dectin-2, a CLR that senses high mannose polysaccharide, in innate immune responses induced by influenza virus hemagglutinin (HA). Treatment of HA with periodate or PNGase F induced lower interleukin (IL)-12p40 secretion by conventional dendritic cells (DCs) compared with the untreated group. In contrast, treatment with O-glycosidase did not affect cytokine production. Green fluorescent protein expression in canonical Dectin-2-transducing cells was approximately 3% - 12% following HA stimulation, except with the A/H1N1pdm09 subtype HA. This expression was markedly reduced in cells possessing mutated amino acids in the carbohydrate recognition domain of Dectin-2, especially following stimulation with HA derived from the A/H3N2 subtype. Interferon (IFN)-α production from CD11c⁺Siglec-H⁺PDCA-1⁺ plasmacytoid DCs was significantly increased in Dectin-2 knockout mice compared with wild-type mice upon stimulation with HA except for the B/Yamagata lineage HA. These results suggested that Dectin-2 is involved in initiating inflammatory responses via mannose polysaccharide on HA. However, other mechanisms may function in the antiviral response, including the type I IFN axis.

关 键 词：C-Type Lectin Receptors Influenza Virus Innate Immunity Type I Interferon 

分 类 号：R73[医药卫生—肿瘤]