Analysis of the mechanism of colonization resistance against pathogenic fungi mediated by commensal bacteria and group3 innate lymphoid cells
Project/Area Number |
19H03465
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 49050:Bacteriology-related
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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)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2019: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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Keywords | 腸内細菌 / Candida albicans / 腸管免疫 / 真菌 |
Outline of Research at the Start |
Candida albicansは腸管内で常在する真菌であるが、腸内細菌叢の攪乱や宿主の免疫力が低下した状況では腸管内で異常に増殖し、危険な感染症の一つである侵襲性カンジダ感染症の要因となる。本研究では、腸内細菌と自然免疫細胞の一つである3型自然リンパ球に着目し、腸管におけるC. albicansの定着・増殖抑制機構の解明を試みる。特に嫌気培養装置を用いて腸内細菌を分離し、C. albicansの増殖を抑制する腸内細菌および腸内細菌由来因子を同定する。本研究は微生物の腸内定着機構という生物学的に重要な意義を有するのみならず、腸内細菌を応用した予防・診断・治療法の開発に繋がることも期待される。
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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.
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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。
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Report
(4 results)
Research Products
(36 results)
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[Journal Article] Subtilase cytotoxin induces a novel form of Lipocalin 2, which promotes Shiga-toxigenic Escherichia coli survival.2020
Author(s)
Yahiro, K., Ogura, K., Goto, Y., Iyoda, S., Kobayashi, T., Takeuchi, H., Ohnishi, M., Moss, J.
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Journal Title
Scientific Reports.
Volume: 10
Issue: 1
Pages: 18943-18943
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Fucosyltransferase 2 induces lung epithelial fucosylation and exacerbates house dust mite-induced airway inflammation.2019
Author(s)
Saku A, Hirose K, Ito T, Iwata A, Sato T, Kaji H, Tamachi T, Suto A, Goto Y, Domino SE, Narimatsu H, Kiyono H, Nakajima H
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Journal Title
J Allergy Clin Immunol.
Volume: 144(3)
Issue: 3
Pages: 698-709
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] CD103hi Treg cells constrain lung fibrosis induced by CD103lo tissue-resident pathogenic CD4 T cells2019
Author(s)
Ichikawa, T.*, Hirahara, K.*, Kokubo, K.*, Kiuchi, M., Aoki, A., Morimoto, Y., Kumagai, J., Onodera, A., Mato, N., Tumes, D., Goto, Y., Hagiwara, K., Inagaki, Y., Sparwasser, T., Tobe, K., and Nakayama, T.
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Journal Title
Nature Immunology
Volume: 20
Issue: 11
Pages: 1469-1480
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Persistent colonization of non-lymphoid tissue-resident macrophages by Stenotrophomonas maltophilia2019
Author(s)
Takahashi Ichiro, Hosomi Koji, Nagatake Takahiro, Tobou Hirokazu, Yamamoto Daiki, Hayashi Ikue, Kurashima Yosuke, Sato Shintaro, Shibata Naoko, Goto Yoshiyuki, Maruyama Fumito, Nakagawa Ichiro, Kuwae Asaomi, Abe Akio, Kunisawa Jun, Kiyono Hiroshi
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Journal Title
International Immunology
Volume: 32
Issue: 2
Pages: 133-141
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Innate lymphoid cells regulate intestinal epithelial cell glycosylation.2014
Author(s)
Goto Y, Obata T, Kunisawa J, Sato S, Ivanov II, Lamichhane A, Takeyama N, Kamioka M, Sakamoto M, Matsuki T, Uematsu S, Akira S, Domino SE, Kulig P, Becher B, Renauld JC, Sasakawa C, Umesaki Y, Benno Y, Kiyono H
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Journal Title
Science
Volume: 345
Issue: 6202
Pages: 1254009-1254009
DOI
Related Report
Peer Reviewed / Open Access
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