Molecular basis for the evasion of host immunity by mycobacteria

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04087
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: Yamasaki Sho 大阪大学, 微生物病研究所, 教授 (40312946)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 抗酸菌 / 免疫抑制

Outline of Final Research Achievements

Mycobacteria-derived lipids recognized by inhibitory immunoreceptors were identified. When we analyzed anti-mycobacterial immune responses of macrophages and dendritic cells from receptor-deficient mice, the production of specific chemokines was selectively up-regulated. We compared the responses to infection between receptor-deficient and wild-type mice, and found that the deficient mice showed enhanced antigen-specific T-cell responses, suggesting that mycobacteria utilize this interaction to evade host immunity. In addition, we identified candidate receptors that recognize PGL. In order to replicate this human anti-mycobacterial responses in mice, we have established BAC transgenic mouse expressing human receptors.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

欠損マウスでは抗酸菌抗原特異的なT細胞応答が増強していることが判明し、結核菌が宿主免疫を回避する分子機構の一端が明らかとなったことにより、抗酸菌、中でもとりわけ近年増加している非定型性抗酸菌に対する治療戦略が広がると期待される。また、ヒトにおける抗酸菌応答をマウスで再現するため、ヒト受容体BACトランスジェニックマウスの樹立に成功したことにより、成人で有効性が低いBCGワクチンの問題点を改善できる可能性があり、より効果の高い結核ワクチンの開発への貢献が期待される。