The effect of aging in pulmonary nontuberculous mycobacterial disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16108
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: University of Tsukuba
• Principal Investigator: Masashi Matsuyama 筑波大学, 附属病院, 病院講師 (30816111)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 肺非結核性抗酸菌症 / 加齢 / Nrf2 / SLPI

Outline of Final Research Achievements

To investigate the effect of aging on pulmonary nontuberculous mycobacterial (NTM) disease, experiments were conducted in which old and young mice were infected with Mycobacterium avium (M. avium) bacteria. The results showed that old mice were more susceptible to NTM infection than young mice. In addition, comprehensive gene expression analysis by RNA-seq was performed in lung tissues two months after infection. The results showed that the expression of secretory leukocyte peptidase inhibitor (SLPI) was lower in the lungs of old mice compared to those of young mice. SLPI was found to have direct antimicrobial activity against M. avium, indicating that SLPI is involved in the control of pulmonary NTM disease. Moreover, Western blotting results suggested that decreased expression of SLPI, which is regulated by Nrf2, is one important factor of exacerbation in pulmonary NTM infection in old mice.

Free Research Field

肺非結核性抗酸菌症

Academic Significance and Societal Importance of the Research Achievements

肺NTM症は高齢者に多くみられ、65歳以上の患者で死亡率が上昇することが報告されているが、その理由は不明であった。我々は、加齢が肺NTM症におよぼす影響の一部を明らかにすることができた。Nrf2に制御されるSLPIの発現低下が、加齢により肺NTM症が悪化する理由の一つであるという事実は、今後の新規治療方法を考慮するのに重要な報告となった。SLPIやNrf2を活性化する薬剤を肺NTM症患者に使用するという可能性は、社会的意義がとても大きい。また、今回の老齢NTM感染マウス肺組織の網羅的遺伝子発現解析の結果は、他の新たなシーズを生み出す可能性も秘めている。