Investigation of host immunity and development of novel immunomodulatory therapies for severe and refractory respiratory tract infections

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08517
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Nagoya University
• Principal Investigator: Shindo Yuichiro 名古屋大学, 医学部附属病院, 病院講師 (60608884)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 重症肺炎 / 術後肺炎 / 肺非結核性抗酸菌症 / 肺MAC症 / 免疫機能障害 / 免疫細胞疲弊 / 免疫療法

Outline of Final Research Achievements

This study was performed using blood samples from patients with severe or refractory respiratory infections including pneumonia and non-tuberculous mycobacterial infection (NTM). In community-acquired pneumonia patients with poor outcome, activation markers on T cells were increased, compared to those with good outcome. However, co-stimulatory molecule expression was decreased in patients with poor outcome. In NTM patients, co-inhibitory molecule expressions were increased compared to healthy controls (HCs). Expression patterns of transcription factors regarding cell proliferation and cytokine production differed between NTM patients and HCs. Furthermore, immune cell functions in NTM patients tended to be declined as disease duration became longer.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

本研究では、最初の侵襲が大きい（感染が重症あるいは外科手術の侵襲度が高い）とその後に免疫細胞疲弊が起こりやすく、またMACのように病原体自体が比較的弱毒の場合は罹病期間が長いほど免疫細胞疲弊を来しやすい傾向がみられた。これらは重症・難治性呼吸器感染症患者の新たな免疫療法ストラテジーを構築するうえで学術的に重要な知見であり、予後不良となる患者を救命するための治療に繋がる社会的意義もある知見である。