The effects of diabetes on the immune response to cryptococcal infection

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16314
• 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): 2021-04-01 – 2023-03-31
• Keywords: クリプトコックス / 糖尿病 / 感染免疫 / T細胞

Outline of Final Research Achievements

Cryptococcus neoformans is a yeast-type opportunistic fungal pathogen, which infects lungs via airborne rote and causes life-threatening meningoencephalitis in immunocompromised hosts. The detailed mechanism of susceptibility to diabetes mellitus (DM), which is a clinically significant risk factor for this infection, is not well known.
In this study, we analyzed the effects of DM on host defense against cryptococcal infection using an appropriate mouse model. In DM mice, the functions of dendritic cell were not changed. On the other hand, DM mice showed decreased Cryptococcus-specific Th1 responses, increased Treg cells, suppressed macrophage activation, and increased T cell exhaustion. These may exacerbate the infection by DM. Moreover, some of these changes were ameliorated by the addition of GSH.

Free Research Field

感染免疫学

Academic Significance and Societal Importance of the Research Achievements

現在、基礎疾患を有する患者における易感染性については世界的に重要な問題である。本研究により、糖尿病ではクリプトコックス特異的なTh1応答の低下とTreg細胞の増加を引き起こし、感染を増悪させていることが明らかとなり、その原因の一端にGSHの変化を含む糖の代謝異常が直接免疫応答を変化させている可能性が示唆された。これらの研究成果は今後、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。