The effects of high-risk conditions on the immune response to cryptococcal infection

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17920
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Tohoku University
• Principal Investigator: Sato Ko 東北大学, 医学系研究科, 助教 (20832124)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: クリプトコックス / 糖尿病 / ステロイド / 感染免疫

Outline of Final Research Achievements

Cryptococcus neoformans is a yeast-type opportunistic fungal pathogen, which infects lungs via an airborne route and causes life-threatening meningoencephalitis in immunocompromised hosts. Diabetes mellitus (DM) and long-term steroid administration are risk factors for this infection, but there are not well known about their direct effects on the immune response.
In this study, we analyzed the effects of these risk factors on the immune response to cryptococcal infection. It was revealed that the DM condition had different effects on the immune response in the acute phase and the chronic phase. The Th1 immune response was enhanced in the acute phase. On the other hand, the fungal burden was increased in the chronic phase with decreasing the Th1 immune response. In addition, long-term steroid administration led to increasing the fungal burden by suppressing the Th1 immune response.

Free Research Field

感染免疫学

Academic Significance and Societal Importance of the Research Achievements

現在、易感染性を呈する疾患は数多く存在するが、クリプトコックス症においてリスク因子が免疫応答に与える直接的な影響については不明な点が多い。
本研究により、慢性糖尿病及び長期ステロイド投与がクリプトコックスに対する免疫応答を抑制することが明らかとなった。特に糖尿病では、急性期と慢性期で異なる結果が得られ、そこには糖の代謝異常が関与する可能性が示唆された。今後、クリプトコックス症の発症予防・新規治療薬の開発につながる可能性が高い。