Analysis of virulence factors of non-tuberculous mycobacteria focus on alveolar macrophages

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K16226
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Infectious disease medicine
• Research Institution: Nagasaki University
• Principal Investigator: IDE Shotaro 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (20773336)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 非結核性抗酸菌 / 抗酸菌 / マクロファージ / NF-κB / Mycobacterium / NTM / MAC / 気管支拡張症

Outline of Final Research Achievements

The aim of this research was to analyze virulence factors of non-tuberculous mycobacteria (NTM) focusing on immune responses to alveolar macrophages (AM) . We collected 64 strains of NTM from patients with pulmonary non-tuberculous mycobacteriosis (pNTM). The NF-κB eGFP reporter lentiviral-tranceduced murine AM were stimulated with these clinical NTM strains in vitro, then activity of NF-κB expressed by luciferase was detected and inflammatory cytokines in supernatants were measured by ELISA. Distinct AM NF-κB activities was observed depending on NTM strains, e.g. M. kansasii and M. abscessus rough morphotype induced high activity of NF-κB. TNF-α production from AM was dependent on NF-κB, although IL-1β was independent. AM NF-κB activity and bronchial dilatation in pNTM showed an inverse correlation. These results suggested that the AM NF-κB response may relates to bronchial inflammation distraction in pNTM.

Free Research Field

感染免疫学

Academic Significance and Societal Importance of the Research Achievements

pNTMは近年本邦で増加しているが、難治性であり長期間の治療を必要とする疾患である。本研究では、肺の重要な免疫細胞であるマクロファージの転写因子NF-κB誘導能が、pNTMの病型を規定しているか明らかにすることを目的とした。NTMの菌種ごとにマクロファージの免疫反応の違いが見られ、それがpNTMの病型に関連している可能性が示唆された。原因微生物と宿主との免疫反応を明らかにすることで、pNTMの病態および増悪因子の理解につながることが期待される。