Novel strategy against invasive pneumococcal diseases by regulating tight junction and bottleneck effect

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08825
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Wakayama Medical University
• Principal Investigator: Kono Masamitsu 和歌山県立医科大学, 医学部, 講師 (20511570)
• Co-Investigator(Kenkyū-buntansha): 杉田 玄 和歌山県立医科大学, 医学部, 講師 (20407274) ; 武田 早織 和歌山県立医科大学, 医学部, 博士研究員 (20644090) ; 村上 大地 和歌山県立医科大学, 医学部, 準客員研究員 (30794218)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 侵襲性肺炎球菌感染症

Outline of Final Research Achievements

The aim of the study was to clarify the roles of the barrier mechanism of the nasal cavity and immune responses by innate immunity and neural networks (transient receptor potential: TRP) in the control of invasive infections. In a co-culture model of epithelial cell lines and pneumococci, we confirmed that pneumococci invade intercellular spaces and proliferate in deeper layers. We also established a model of spontaneous arising sepsis caused by pneumococcal nasal carriage. The incidence of bacteremia was high in TLR9 KO mice with pneumococcal single infection, however, with influenza superinfection, TLR3 KO mice and TRPV4 KO mice showed high bacteremia incidence. In the development of invasive pneumococcal infections, innate immunity and TRP mechanisms were considered to control the development of invasive infections.

Free Research Field

耳鼻咽喉科

Academic Significance and Societal Importance of the Research Achievements

本研究では、IPD発症を制御する鼻腔バリア機構の機序解明を目的とする。肺炎球菌による菌血症は肺感染を介さずに発症することも多く、突然の発熱と全身状態悪化をきたししばしば致死的となる重篤な感染症である。本研究では、気道上皮細胞株を用いたin vitroモデルと研究代表者がこれまでに確立した侵襲性肺炎球菌感染症自然発症モデルを用いたin vivoモデルを組み合わせた展開を行った。気道上皮細胞系の維持と恒常性維持における免疫機構に着目した治療戦略の樹立は世界的に大きなインパクトがあるものと考える。