Regulation of innate immune response to mycobacteria through the recognition of immunoregulating cell wall lipids by ITAM-coupled receptors

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04729
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: Kagoshima University
• Principal Investigator: hara hiromitsu 鹿児島大学, 医歯学域医学系, 教授 (20392079)
• Co-Investigator(Renkei-kenkyūsha): YAMASAKI Sho 大阪大学, 微生物病研究所, 教授 (40312946) ; MATSUZAKI Goro 琉球大学, 熱帯生物圏研究センター, 教授 (30229455) ; KIYOHARA Hideyasu 日本BCG研究所, 第一研究科部, 研究員 (10514581) ; IIZASA Eiichi 鹿児島大学, 医歯学総合研究科, 助教 (20631998) ; MAENAKA Katsumi 北海道大学, 薬学研究科, 教授 (10322752) ; MIYAZAKI Jun 国際医療福祉大学, 医学部, 教授 (10550246)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 抗酸菌 / ITAM / CLR / 自然免疫 / マクロファージ / 脂質

Outline of Final Research Achievements

Mycobacterial cell wall lipids have immune-stimulating or modulating activities. Several C-type lectin receptors associated with immunoreceptor tyrosine-based activation motif (ITAM)-bearing adaptor FcRγ recognize mycobacterial glycolipids and play important roles in anti-mycobacterial immunity. On the other hand, previous studies suggested immunomodulatory role of DAP12, another ITAM-bearing adaptor, in anti-mycobacterial immunity, implicating the presence of DAP12-associated receptors that might recognize immunomodulatory ligands in mycobacteria. We identified two novel ITAM-coupled receptors that recognize the immunomodulatory mycobacterial lipids mycolate (MA) and phenolic glycolipids (PGL). Deficiency of these receptors in macrophages abrogated the response to these lipids. Activation of the MA receptor recruited mycobacterium permissive macrophages. Loss of the MA receptor enhanced mincle-induced inflammation in vivo and accelerated clearance of M. bovis BCG infected in mice.

Free Research Field

免疫学