The role of transient receptor potential channels in developing invasive pneumococcal infection.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08959
• 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: Sugita Gen 和歌山県立医科大学, 医学部, 講師 (20407274)
• Co-Investigator(Kenkyū-buntansha): 大谷 真喜子 和歌山県立医科大学, 医学部, 講師 (00795594) ; 河野 正充 和歌山県立医科大学, 医学部, 講師 (20511570) ; 保富 宗城 和歌山県立医科大学, 医学部, 教授 (90336892)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肺炎球菌 / 侵襲性肺炎球菌感染症 / TRP channel / インフルエンザウイルス

Outline of Final Research Achievements

Transient receptor potential channels, neuronal stimulations widely known to be associated with thermal responses, pain induction and osmoregulation, have been shown in recent studies to have underlying mechanisms associated with inflammatory responses. It may vary among types of channels, however, it is not known how TRP channels function during pneumococcal infections. This study examined the role of Transient receptor potential Vanilloid (TRPV) 1 and TRPV4 for nasal colonization and subsequent development of invasive disease in a mouse model. Both TRPV1 and TRPV4 channels were related to regulation of the development of invasive diseases. In particular, the influx of neutrophils in the nasal cavity and the bactericidal activity were suppressed among TRPV4 knockout mice. This may lead to severe pneumonia, causing high mortality during influenza virus co-infection. Regulating host immune responses with TRP channels would be a novel strategy against various pathogenic microorganisms.

Free Research Field

耳鼻咽喉科

Academic Significance and Societal Importance of the Research Achievements

TRPチャネルは生体の恒常性を維持する非常に重要な機構の一つである。近年、病原微生物により惹起された炎症におけるTRPチャネルの関与が示唆されていたが、上気道感染症から全身感染症まで様々な感染症の原因菌となる肺炎球菌との関連については報告がなかった。本研究では侵襲性肺炎球菌感染症において、TRPチャネルが疾患の重症化を制御していることを動物モデルにより世界で初めて証明し、肺炎球菌感染症の重症化を予防するための新たな治療法開発における重要な基礎的知見を提供した。