| Budget Amount *help |
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| 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.
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