PMID- 27887882 OWN - NLM STAT- MEDLINE DCOM- 20170913 LR - 20171217 IS - 1097-4180 (Electronic) IS - 1074-7613 (Linking) VI - 45 IP - 6 DP - 2016 Dec 20 TI - C-Type Lectin Receptor DCAR Recognizes Mycobacterial Phosphatidyl-Inositol Mannosides to Promote a Th1 Response during Infection. PG - 1245-1257 LID - S1074-7613(16)30403-4 [pii] LID - 10.1016/j.immuni.2016.10.012 [doi] AB - 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 FcRgamma-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 FcRgamma abrogated MCP-1 production. Upon mycobacterial infection, Clec4b1-deficient mice showed reduced numbers of monocyte-derived inflammatory cells at the infection site, impaired IFNgamma 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. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Toyonaga, Kenji AU - Toyonaga K AD - Division of Molecular Immunology, Research Center for Infectious Diseases, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. FAU - Torigoe, Shota AU - Torigoe S AD - Division of Molecular Immunology, Research Center for Infectious Diseases, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. FAU - Motomura, Yoshitomo AU - Motomura Y AD - Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. FAU - Kamichi, Takane AU - Kamichi T AD - 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. FAU - Hayashi, Jennifer M AU - Hayashi JM AD - Department of Microbiology, University of Massachusetts, Amherst, MA 01003, USA. FAU - Morita, Yasu S AU - Morita YS AD - Department of Microbiology, University of Massachusetts, Amherst, MA 01003, USA. FAU - Noguchi, Naoto AU - Noguchi N AD - Division of Host Defense, Research Center for Infectious Diseases, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. FAU - Chuma, Yasushi AU - Chuma Y AD - Japan BCG Laboratory, Kiyose 204-0022, Japan. FAU - Kiyohara, Hideyasu AU - Kiyohara H AD - Japan BCG Laboratory, Kiyose 204-0022, Japan. FAU - Matsuo, Kazuhiro AU - Matsuo K AD - Japan BCG Laboratory, Kiyose 204-0022, Japan. FAU - Tanaka, Hiroshi AU - Tanaka H AD - Department of Applied Chemistry, Graduate School of Science and Technology, Tokyo Institute of Technology, Tokyo 152-8552, Japan. FAU - Nakagawa, Yoshiko AU - Nakagawa Y AD - Center for Animal Resources and Development, Kumamoto University, Kumamoto 860-0811, Japan. FAU - Sakuma, Tetsushi AU - Sakuma T AD - Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima 739-8526, Japan. FAU - Ohmuraya, Masaki AU - Ohmuraya M AD - Center for Animal Resources and Development, Kumamoto University, Kumamoto 860-0811, Japan. FAU - Yamamoto, Takashi AU - Yamamoto T AD - Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima 739-8526, Japan. FAU - Umemura, Masayuki AU - Umemura M AD - 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. FAU - Matsuzaki, Goro AU - Matsuzaki G AD - 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. FAU - Yoshikai, Yasunobu AU - Yoshikai Y AD - Division of Host Defense, Research Center for Infectious Diseases, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. FAU - Yano, Ikuya AU - Yano I AD - Japan BCG Laboratory, Kiyose 204-0022, Japan. FAU - Miyamoto, Tomofumi AU - Miyamoto T AD - Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan. FAU - Yamasaki, Sho AU - Yamasaki S AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161122 PL - United States TA - Immunity JT - Immunity JID - 9432918 RN - 0 (Bacterial Proteins) RN - 0 (Lectins, C-Type) RN - 0 (Phosphatidylinositols) RN - 0 (Receptors, Immunologic) RN - 0 (dendritic cell immunoactivating receptor, mouse) RN - 0 (phosphatidylinositol mannoside) SB - IM MH - Animals MH - Bacterial Proteins/*immunology MH - Lectins, C-Type/*immunology MH - Lymphocyte Activation/immunology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mycobacterium/immunology MH - Mycobacterium Infections/immunology MH - Phosphatidylinositols/*immunology MH - Receptors, Immunologic/*immunology MH - Th1 Cells/*immunology EDAT- 2016/11/27 06:00 MHDA- 2017/09/14 06:00 CRDT- 2016/11/27 06:00 PHST- 2016/04/10 00:00 [received] PHST- 2016/07/25 00:00 [revised] PHST- 2016/08/26 00:00 [accepted] PHST- 2016/11/27 06:00 [pubmed] PHST- 2017/09/14 06:00 [medline] PHST- 2016/11/27 06:00 [entrez] AID - S1074-7613(16)30403-4 [pii] AID - 10.1016/j.immuni.2016.10.012 [doi] PST - ppublish SO - Immunity. 2016 Dec 20;45(6):1245-1257. doi: 10.1016/j.immuni.2016.10.012. Epub 2016 Nov 22.