2022 Fiscal Year Final Research Report
Phenotypic analysis of Dirofilaria immitis infetion in LRIM18-knockout Aedes aegypti
| Project/Area Number |
20K15656
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 42020:Veterinary medical science-related
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| Research Institution | Fujita Health University (2021-2022)
Obihiro University of Agriculture and Veterinary Medicine (2020) |
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Principal Investigator |
Shirozu Takahiro 藤田医科大学, 病態モデル先端医学研究センター, 助教 (80804608)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | ネッタイシマカ / 犬糸状虫 / ゲノム編集 / ベクターコントロール / 自然免疫 |
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| Outline of Final Research Achievements |
Susceptible (S) and resistance (R) strains to Dirofilaria immitis infection were identified in Aedes aegypti Liverpool strain. RNA-seq and RNAi screening analysis showed that Leucine-rich immune protein (LRIM) 18 was identified as a target gene related to vectorial capacity for D. immitis in mosquitoes. In this study, LRIM18 knockout (KO) mosquitoes were generated by genome editing using CRISPR/Cas9 and we analyzed D. immitis infection phenotype to elucidate the function of LRIM18 in the host response. Comparative analysis between KO and wild type in S showed that the number of infective third-stage larvae was significantly low in the head and thorax in KO-S. Moreover, the number of undeveloped larvae was significantly high in the abdomen in KO-S. RNA-seq analysis showed the immune system-related genes expression increased in the Malpighian tubules in KO-S. In summary, our findings suggests that KO of LRIM18 in mosquitoes may contribute to the control of D. immitis.
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| Free Research Field |
寄生虫学
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| Academic Significance and Societal Importance of the Research Achievements |
蚊媒介性感染症であるフィラリア症は「顧みられない熱帯病」の一つで、開発途上国を中心に蔓延しており、世界の感染者数は約5000万人以上とされる。また、犬のフィラリア(犬糸状虫)症は致死に至ることもあり、獣医学領域においても対策が必要な感染症である。致死性の高いマラリア、デング熱などと比べて、開発途上国やペットで問題となるフィラリア症に関する研究進展状況は芳しくない。犬糸状虫とネッタイシマカをフィラリア感染モデルとした本研究で、LRIM18のKOにより蚊の犬糸状虫媒介能が抑制されることが示唆された。本研究成果は、フィラリアを媒介しない蚊の作出による感染症制御に向けた学術基盤になることが期待される。
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