title: C-Type Lectin Receptor DCAR Recognizes Mycobacterial Phosphatidyl-Inositol Mannosides to Promote a Th1 Response during Infection.
abstract: Phosphatidyl-inositol mannosides (PIM) are glycolipids unique to mycobacteria and other related bacteria that stimulate host immune responses and are implicated in mycobacteria pathogenicity. Here, we found that the FcRγ-coupled C-type lectin receptor DCAR (dendritic cell immunoactivating receptor; gene symbol Clec4b1) is a direct receptor for PIM. Mycobacteria activated reporter cells expressing DCAR, and delipidation of mycobacteria abolished this activity. Acylated PIMs purified from mycobacteria were identified as ligands for DCAR. DCAR was predominantly expressed in small peritoneal macrophages and monocyte-derived inflammatory cells in lungs and spleen. These cells produced monocyte chemoattractant protein-1 (MCP-1) upon PIM treatment, and absence of DCAR or FcRγ abrogated MCP-1 production. Upon mycobacterial infection, Clec4b1-deficient mice showed reduced numbers of monocyte-derived inflammatory cells at the infection site, impaired IFNγ production by T cells, and an increased bacterial load. Thus, DCAR is a critical receptor for PIM that functions to promote T cell responses against mycobacteria.
authors.affiliation: Division of Molecular Immunology, Research Center for Infectious Diseases, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Toyonaga
authors.affiliation: Division of Molecular Immunology, Research Center for Infectious Diseases, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Torigoe
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Motomura
authors.affiliation: Division of Molecular Immunology, Research Center for Infectious Diseases, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Takane
authors.initials: T
authors.lastname: Kamichi
authors.affiliation: Department of Microbiology, University of Massachusetts, Amherst, MA 01003, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Hayashi
authors.affiliation: Department of Microbiology, University of Massachusetts, Amherst, MA 01003, USA.
authors.forename: Yasu S
authors.initials: YS
authors.lastname: Morita
authors.affiliation: Division of Host Defense, Research Center for Infectious Diseases, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Noguchi
authors.affiliation: Japan BCG Laboratory, Kiyose 204-0022, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Chuma
authors.affiliation: Japan BCG Laboratory, Kiyose 204-0022, Japan.
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Kiyohara
authors.affiliation: Japan BCG Laboratory, Kiyose 204-0022, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Department of Applied Chemistry, Graduate School of Science and Technology, Tokyo Institute of Technology, Tokyo 152-8552, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Center for Animal Resources and Development, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima 739-8526, Japan.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Sakuma
authors.affiliation: Center for Animal Resources and Development, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ohmuraya
authors.affiliation: Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima 739-8526, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Molecular Microbiology Group, Department of Infectious Diseases, Tropical Biosphere Research Center, and Department of Host Defense, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0213, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Umemura
authors.affiliation: Molecular Microbiology Group, Department of Infectious Diseases, Tropical Biosphere Research Center, and Department of Host Defense, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0213, Japan.
authors.forename: Goro
authors.initials: G
authors.lastname: Matsuzaki
authors.affiliation: Division of Host Defense, Research Center for Infectious Diseases, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yoshikai
authors.affiliation: Japan BCG Laboratory, Kiyose 204-0022, Japan.
authors.forename: Ikuya
authors.initials: I
authors.lastname: Yano
authors.affiliation: Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Miyamoto
authors.affiliation: Division of Molecular Immunology, Research Center for Infectious Diseases, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan. Electronic address: yamasaki@bioreg.kyushu-u.ac.jp.
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009161:Mycobacterium / Q000276:immunology; D009164:Mycobacterium Infections / Q000276:immunology; D010716:Phosphatidylinositols / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D037181:Lectins, C-Type; D010716:Phosphatidylinositols; D011971:Receptors, Immunologic; C477518:dendritic cell immunoactivating receptor, mouse; C034154:phosphatidylinositol mannoside