Role of P-body in host translation control during parasite infection
| Project/Area Number |
17K08782
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Gunma University |
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Principal Investigator |
Seto Eri 群馬大学, 大学院医学系研究科, 助教 (40431382)
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| Project Period (FY) |
2017-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 感染応答 / RNA顆粒 / P－body / Trypanosoma cruzi / P-body / mRNP / 感染症 / 寄生虫 |
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| Outline of Final Research Achievements |
P-bodies (PBs) are cytoplasmic messenger ribonucleoprotein (mRNP) granules mainly composed of mRNAs and proteins involved in translation repression and mRNA decay. To elucidate the role of PBs, which are formed in the early stages of infection with a protozoan parasite Trypanosoma cruzi (T. cruzi), in regulating host mRNA metabolism, we analyzed the impact of PB depletion on host transcriptome during T. cruzi infection. The results indicated that the expression of inflammatory cytokines and activation of innate immune-related signaling pathways were enhanced in PB-defective cells compared to wild-type cells. Our results show for the first time that T. cruzi may establish infection by negatively regulating the host innate immune response through the promotion of PB assembly.
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| Academic Significance and Societal Importance of the Research Achievements |
病原体が感染した細胞では、迅速かつダイナミックなmRNA 代謝調節により感染応答が惹起されると考えられるが、その制御機構については不明な点が多い。本研究により、原虫感染時に自然免疫応答に重要な複数の遺伝子の発現がPB形成依存的に抑制されていることが明らかとなった。このように、原虫が宿主の感染応答をPBによる遺伝子発現調節を利用して回避していることを示唆する報告はこれまでになく、mRNA代謝調節を介した宿主病原体相互作用について理解を深める一助となった。また、同定されたターゲット遺伝子のPBによる発現調節機構のさらなる解明により、その知見を基盤とした治療薬開発への応用につながることも期待できる。
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Report
(7 results)
Research Products
(20 results)
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[Journal Article] Inhibition of autolysosome formation in host autophagy by Trypanosma cruzi infection.2017
Author(s)
Onizuka, Y., Takahashi, C., Uematsu, A., Shinjo, S., Seto, E., and Nalajima-Shimada, J.
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Journal Title
Acta Tropica
Volume: 21
Pages: 57-62
DOI
Related Report
Peer Reviewed
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