tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Chikako Tomiyama[SUP] 2 [/SUP], Ko Sato[SUP] 3 [/SUP], Jun Kasamatsu[SUP] 3 [/SUP], Kazuki Takano[SUP] 4 [/SUP], Aya Umeki[SUP] 4 [/SUP], Nana Nakahata[SUP] 4 [/SUP], Tomomitsu Miyasaka[SUP] 5 [/SUP], Emi Kanno[SUP] 6 [/SUP], Hiromasa Tanno[SUP] 6 [/SUP], Sho Yamasaki[SUP] 7 [/SUP], Shinobu Saijo[SUP] 8 [/SUP], Yoichiro Iwakura[SUP] 9 [/SUP], Keiko Ishii[SUP] 4 [/SUP], Kazuyoshi Kawakami[SUP] 3 4 [/SUP]
Affiliations
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.
. 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[SUP] 1 [/SUP], Chikako Tomiyama[SUP] 2 [/SUP], Ko Sato[SUP] 3 [/SUP], Jun Kasamatsu[SUP] 3 [/SUP], Kazuki Takano[SUP] 4 [/SUP], Aya Umeki[SUP] 4 [/SUP], Nana Nakahata[SUP] 4 [/SUP], Tomomitsu Miyasaka[SUP] 5 [/SUP], Emi Kanno[SUP] 6 [/SUP], Hiromasa Tanno[SUP] 6 [/SUP], Sho Yamasaki[SUP] 7 [/SUP], Shinobu Saijo[SUP] 8 [/SUP], Yoichiro Iwakura[SUP] 9 [/SUP], Keiko Ishii[SUP] 4 [/SUP], Kazuyoshi Kawakami[SUP] 3 4 [/SUP]
Affiliations
- PMID: 33840686
- DOI: 10.2220/biomedres.42.53
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.