Regulation of immune responses via C-type lectin receptor family that recognize mycobacteria

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293099
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: Kyushu University
• Principal Investigator: Yamasaki Sho 九州大学, 生体防御医学研究所, 教授 (40312946)
• Co-Investigator(Kenkyū-buntansha): 大村谷 昌樹 熊本大学, 学内共同利用施設等, 准教授 (60398229)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: C型レクチン / 自然免疫 / 細菌感染 / 糖脂質

Outline of Final Research Achievements

Phosphatidyl-inositol mannosides (PIM) are unique mycobacterial glycolipids that stimulate host immune responses. Mycobacteria activated reporter cells expressing DCAR and delipidation of mycobacteria abolished this activity. Further, tri- and tetra-acylated PIMs (AcPIM2 and Ac2PIM2) purified from mycobacteria lipids were ligands for DCAR. DCAR was predominantly expressed in small peritoneal macrophages (SPMs) and monocyte-derived inflammatory cells in lungs and spleen. PIM treatment induced these cells to produce MCP-1, and production of MCP-1 was abrogated in the absence of DCAR or FcRγ. Upon mycobacterial infection, DCAR-deficient mice showed reduced numbers of monocyte-derived inflammatory cells at the infection site, impaired IFNγ production by CD4+ T cells, and an increased bacterial load. These results demonstrate that DCAR is a critical receptor for mycobacterial PIM and functions to promote Th1 responses against mycobacteria.

Free Research Field

免疫学