Analysis of the mechanism of colonization resistance against pathogenic fungi mediated by commensal bacteria and group3 innate lymphoid cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03465
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Chiba University
• Principal Investigator: Goto Yoshiyuki 千葉大学, 真菌医学研究センター, 准教授 (10755523)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 腸内細菌

Outline of Final Research Achievements

In this study, we tried to identify the roles of intestinal commensal bacteria and host immune cells that inhibit intestinal colonization of pathogenic fungi. As a result, we found that specific intestinal bacteria inhibit the intestinal colonization of Candida albicans in vivo. The specific commensal bacteria produced a water-soluble facors that inhibits the growth of other several Candida species. Furthermore, it was identified that group 3 innate lymphoid cells inhibit the intestinal colonization of C. albicans by promoting the formation of secondary lymphoid organs through LTa and inducing the differentiation and proliferation of CD4 positive T cells. From these results, it is identified that intestinal bacteria and host immune cells play a protective barrier system that inhibits intestinal colonization of pathogenic fungi.

Free Research Field

粘膜免疫学

Academic Significance and Societal Importance of the Research Achievements

腸内細菌は種々の病原性微生物の腸管定着を阻害する効果、”colonization resistance”効果を有することは以前より知られていたものの、そのメカニズムの多くは不明であった。本研究により、腸内細菌よる病原性真菌の定着阻害機構の一端が明らかとなった。さらに、宿主免疫細胞も病原性真菌の定着を阻害していることを明らかになった。病原性真菌は、HIV感染、臓器移植、抗ガン剤投与患者、高齢者など免疫力が低下したヒトにおいて、難治性感染症である侵襲性真菌症を誘導する微生物であり、本研究において見出した知見が新規抗真菌治療方法の確立に繋がることが期待される。