[ODP-180] Perturbation of host protective immunity by mycobacterial carbohydrates
Mycobacteria possess various components in its cell wall. Hydrophobic components induce immune activation through C-type lectin receptors (CLRs) such as Mincle and DCAR. Hydrophilic components are also included in the mycobacterial cell wall, however the receptors for the components and its function are still elusive. To identify the innate receptors, we stimulated NFAT-GFP reporter cells expressing various CLRs with hydrophilic extract from M. tuberculosis. Cells bearing MRCL showed high GFP expression in response to the mycobacterial extract. Purification of a ligand from the extract using ethanol precipitate, anion exchange column chromatography increased specific activity of hydrophilic extract, which was not sensitive to DNase, RNase and trypsin and was detected by phenol-sulfuric acid method. Gel filtration column chromatography showed the ligand possessed high molecular weight, implying that the active fraction includes polysaccharides. To examine the role of MRCL through recognition of the ligand in mycobacterial infection, WT and MRCL-deficient mice were exposed to M. tuberculosis by aerosol infection. MRCL-deficient mice showed the less bacterial loads in the lungs at 4 weeks after infection, compared with WT mice.These results suggest that recognition of mycobacterial polysaccharides through MRCL perturbs host protective immunity.