A innate immune defense system against Mycobacterium avium pulmonary disease based on intracellular pH homeostasis

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17205
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Yoshida Mitsunori 国立感染症研究所, ハンセン病研究センター 感染制御部, 主任研究官 (70772630)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 非結核性抗酸菌症 / 発症機序

Outline of Final Research Achievements

The aim of this study was to test the hypothesis that reduced CHP2 gene expression inhibits the inflammatory response and bactericidal mechanisms based on intracellular pH regulation during pulmonary MAC infection. In human alveolar epithelial cell lines, CHP2 knockdown tended to increase the infection efficiency of MAC strains, but no significant difference in intracellular bacterial content after infection was observed. To test the possibility that CHP2 is involved in the bactericidal mechanism of MAC in vivo, CHP2 knockout mice were generated. However, planned tests could not be carried out because the reproductive efficiency of the homozygous individuals was reduced.

Free Research Field

ゲノム微生物学

Academic Significance and Societal Importance of the Research Achievements

近年の先進国を中心とした肺MAC症患者の急増から、肺MAC症の発症機序の解明と新たな診断方法および治療方法の開発は、今後さらに重要性が増すことが予想される研究分野である。本研究から、CHP2遺伝子がヒトの肺胞上皮細胞におけるMAC菌株の感染効率に関与している可能性が示唆された。将来的に、CHP2遺伝子が関与する肺MAC症の発症機序を証明することができれば、得られた知見に基づいた創薬研究、診断方法や治療法開発などへの展開も十分に期待できる。