RRC ID 19086
著者 Takahara K, Tokieda S, Nagaoka K, Inaba K.
タイトル Efficient capture of Candida albicans and zymosan by SIGNR1 augments TLR2-dependent TNF-α production.
ジャーナル Int Immunol
Abstract SIGNR1, a mouse C-type lectin, binds various pathogens, including Candida albicans. In this study, we explore the impact of SIGNR1 in the recognition of C. albicans/zymosan and the subsequent tumor necrosis factor (TNF)-α production using SIGNR1-transfected RAW264.7 (RAW-SIGNR1) cells and resident peritoneal macrophages. Compared with RAW-control cells, RAW-SIGNR1 cells dramatically enhanced TNF-α production upon the stimulation with heat-killed C. albicans and zymosan. Recognition of microbes via carbohydrate recognition domain (CRD) of SIGNR1 was crucial for the enhanced TNF-α production. Consistently, such an enhancement was significantly decreased by anti-SIGNR1 mAb. Laminarin, antagonistic Dectin-1 ligand, cooperated to further diminish the response, although no effect was observed by itself in RAW-SIGNR1 cells. However, it moderately reduced the response of RAW-control cells. Zymosan depleted of toll-like receptor (TLR) ligands decreased the response, even though it was recognized by SIGNR1 and Dectin-1. Moreover, antagonistic anti-TLR2 abolished the response, suggesting that TNF-α production largely relies on TLR2-mediated signaling. Resident peritoneal macrophages expressing SIGNR1 predominantly captured zymosan injected intra-peritoneally and produced TNF-α, which was dependent on TLR2 and partly inhibited by anti-SIGNR1 mAb. Finally, physical association of SIGNR1 with the extracellular portion of TLR2 through CRD was confirmed by immunoprecipitation using various deletion mutants. These results suggest that SIGNR1 recognizing microbes participates in the enhanced TNF-α production by Mϕ in cooperation with TLR2.
巻・号 24(2)
ページ 89-96
公開日 2012-2-1
DOI 10.1093/intimm/dxr103
PII dxr103
PMID 22207132
MeSH Animals Antibodies, Monoclonal / pharmacology Antigens, Bacterial / immunology Candida albicans / immunology* Cell Adhesion Molecules / genetics Cell Adhesion Molecules / immunology Cell Adhesion Molecules / metabolism* Cell Line Host-Pathogen Interactions / drug effects Lectins, C-Type / genetics Lectins, C-Type / immunology Lectins, C-Type / metabolism* Macrophages, Peritoneal / drug effects Macrophages, Peritoneal / immunology Macrophages, Peritoneal / metabolism* Macrophages, Peritoneal / pathology Mice Mice, Inbred BALB C Mice, Knockout Receptors, Cell Surface / genetics Receptors, Cell Surface / immunology Receptors, Cell Surface / metabolism* Signal Transduction / immunology Toll-Like Receptor 2 / genetics Toll-Like Receptor 2 / immunology Toll-Like Receptor 2 / metabolism* Transgenes / genetics Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / immunology Tumor Necrosis Factor-alpha / metabolism* Up-Regulation / drug effects Zymosan / administration & dosage Zymosan / immunology
IF 3.519
引用数 15
WOS 分野 IMMUNOLOGY
リソース情報
一般微生物 JCM 1542