title: Difference in fine specificity to polysaccharides of Candida albicans mannoprotein between mouse SIGNR1 and human DC-SIGN.
abstract: C-type lectin SIGNR1 directly recognizes Candida albicans and zymosan and has been considered to share properties of polysaccharide recognition with human DC-SIGN (hDC-SIGN). However, the precise specificity of SIGNR1 and the difference from that of hDC-SIGN remain to be elucidated. We prepared soluble forms of SIGNR1 and hDC-SIGN and conducted experiments to examine their respective specificities. Soluble SIGNR1 (sSIGNR1) bound several types of live C. albicans clinical isolate strains in an EDTA-sensitive manner. Inhibition analyses of sSIGNR1 binding by glycans from various yeast strains demonstrated that SIGNR1 preferentially recognizes N-glycan α-mannose side chains in Candida mannoproteins, as reported in hDC-SIGN. Unlike shDC-SIGN, however, sSIGNR1 recognized not only Saccharomyces cerevisiae, but also C. albicans J-1012 glycan, even after α-mannosidase treatment that leaves only β1,2-mannose-capped α-mannose side chains. In addition, glycomicroarray analyses showed that sSIGNR1 binds mannans from C. albicans and S. cerevisiae but does not recognize Lewis(a/b/x/y) antigen polysaccharides as in shDC-SIGN. Consistent with these results, RAW264.7 cells expressing hDC-SIGN in which the carbohydrate recognition domain (CRD) was replaced with that of SIGNR1 (RAW-chimera) produced comparable amounts of interleukin 10 (IL-10) in response to glycans from C. albicans and S. cerevisiae, but those expressing hDC-SIGN produced less IL-10 in response to S. cerevisiae than C. albicans. Furthermore, RAW-hDC-SIGN cells remarkably reduced IL-10 production after α-mannosidase treatment compared with RAW-chimera cells. These results indicate that SIGNR1 recognizes C. albicans/yeast through a specificity partly distinct from that of its homologue hDC-SIGN.
authors.affiliation: Department of Animal Development and Physiology, Graduate School of Biostudies, and CREST, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takahara
authors.forename: Takuya
authors.initials: T
authors.lastname: Arita
authors.forename: Sumika
authors.initials: S
authors.lastname: Tokieda
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shibata
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Okawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tateno
authors.forename: Jun
authors.initials: J
authors.lastname: Hirabayashi
authors.forename: Kayo
authors.initials: K
authors.lastname: Inaba
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000276:immunology* / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D008264:Macrophages; D051379:Mice; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011994:Recombinant Proteins; D012441:Saccharomyces cerevisiae; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D016753:Interleukin-10; D037181:Lectins, C-Type; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin