title: Characterization of the receptors for mycobacterial cord factor in Guinea pig.
abstract: Guinea pig is a widely used animal for research and development of tuberculosis vaccines, since its pathological disease process is similar to that present in humans. We have previously reported that two C-type lectin receptors, Mincle (macrophage inducible C-type lectin, also called Clec4e) and MCL (macrophage C-type lectin, also called Clec4d), recognize the mycobacterial cord factor, trehalose-6,6'-dimycolate (TDM). Here, we characterized the function of the guinea pig homologue of Mincle (gpMincle) and MCL (gpMCL). gpMincle directly bound to TDM and transduced an activating signal through ITAM-bearing adaptor molecule, FcRγ. Whereas, gpMCL lacked C-terminus and failed to bind to TDM. mRNA expression of gpMincle was detected in the spleen, lymph nodes and peritoneal macrophages and it was strongly up-regulated upon stimulation of zymosan and TDM. The surface expression of gpMincle was detected on activated macrophages by a newly established monoclonal antibody that also possesses a blocking activity. This antibody potently suppressed TNF production in BCG-infected macrophages. Collectively, gpMincle is the TDM receptor in the guinea pig and TDM-Mincle axis is involved in host immune responses against mycobacteria.
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Toyonaga
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan ; Research Center for Advanced Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Miyake
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan ; Research Center for Advanced Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003311:Cord Factors / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006168:Guinea Pigs; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D009163:Mycobacterium bovis / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D003311:Cord Factors; D037181:Lectins, C-Type; D012333:RNA, Messenger; D011961:Receptors, Fc