title: C-type lectin SIGNR1 enhances cellular oxidative burst response against C. albicans in cooperation with Dectin-1.
abstract: We investigated the role of SIGNR1 in the recognition of Candida albicans and the subsequent cellular oxidative burst response. Soluble SIGNR1 (sSIGNR1) tetramer bound equally to zymosan and both heat-killed (HK) and live C. albicans in an EDTA-sensitive manner, whereas sDectin-1 tetramer predominantly bound to zymosan and HK-microbes in an EDTA-independent manner. In cellular response, enhanced oxidative burst was observed in RAW264.7 cells expressing SIGNR1 (RAW-SIGNR1) compared with RAW-control cells upon stimulation with HK-C. albicans and zymosan. This response was independent of TLR2 and the cytosolic portion of SIGNR1 but dependent on the recognition by SIGNR1 via carbohydrate recognition domain. Antagonistic laminarin and anti-Dectin-1 mAb cooperatively reduced the response with mannan and anti-SIGNR1 mAb, respectively, although they had no effect by themselves. Moreover, oxidative response and bactericidal activity largely relied on Syk-mediated signaling. RAW-SIGNR1 cells not only captured microbes more efficiently but also showed higher responses than RAW-control cells. Similar enhanced responses were observed in SIGNR-1-expressing resident peritoneal Mϕ. Interestingly, Dectin-1 was recruited to the phagosomal membrane upon the stimulation and physically associated with SIGNR1. These results suggest that SIGNR1 plays a significant role in inducing oxidative response to C. albicans by Syk-dependent signaling, possibly through Dectin-1.
authors.affiliation: Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takahara
authors.forename: Sumika
authors.initials: S
authors.lastname: Tokieda
authors.forename: Koji
authors.initials: K
authors.lastname: Nagaoka
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Takeda
authors.forename: Yukino
authors.initials: Y
authors.lastname: Kimura
authors.forename: Kayo
authors.initials: K
authors.lastname: Inaba
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002176:Candida albicans / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D004492:Edetic Acid; D005260:Female; D005936:Glucans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology; D008351:Mannans; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism*; D010588:Phagosomes; D016133:Polymerase Chain Reaction; D011134:Polysaccharides / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D016897:Respiratory Burst; D015398:Signal Transduction; D000072377:Syk Kinase; D051195:Toll-Like Receptor 2 / Q000276:immunology; D015054:Zymosan / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000099181:Dectin-1
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D004492:Edetic Acid; D005936:Glucans; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008351:Mannans; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011134:Polysaccharides; D011505:Protein-Tyrosine Kinases; D011956:Receptors, Cell Surface; D000072377:Syk Kinase; D051195:Toll-Like Receptor 2; D015054:Zymosan; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000099181:Dectin-1; C493486:Tlr2 protein, mouse; C008247:laminaran; C000606897:Syk protein, mouse