[ODP6F] f. 免疫機構・ワクチン開発

[ODP-180] 結核菌は親水性成分を用いて宿主免疫を撹乱させる。

○鳥越 祥太¹，河野 央²，水野 悟²，松尾 和浩²，山崎 晶^1,3,4,5 (¹大阪大学・微生物病研究所・分子免疫制御分野，²日本ビーシージー製造株式会社，³大阪大学・免疫学フロンティア研究センター・分子免疫学，⁴九州大学・生体防御医学研究所・システム免疫学統合研究センター・防御分子構築学分野，⁵千葉大学・真菌医学研究センター・感染免疫分野・宿主応答プロジェクト)

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.