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博士論文
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DOI[info:doi/10.1186/s12931-020-01555-1]のデータに遷移します
Influenza A virus enhances ciliary activity and mucociliary clearance via TLR3 in airway epithelium
- 国立国会図書館永続的識別子
- info:ndljp/pid/11720315
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- doctoral医学系研究科Background: Viral respiratory tract infections, such as influenza A virus (IAV), are common and life-threatening illnesses worldwide. Th...
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デジタル
- 資料種別
- 博士論文
- ISSN
- 1465-9921
- タイトル
- 巻次・部編番号
- 21
- 著者・編者
- 神谷, 陽輔
- 著者標目
- 出版事項
- 出版年月日等
- 2020-10-27
- 出版年(W3CDTF)
- 2020-10-27
- 並列タイトル等
- A型インフルエンザウイルスは、気道上皮のTLR3を介して線毛活性と粘液線毛クリアランスを増強する
- タイトル(掲載誌)
- Respiratory Research
- 授与機関名
- 浜松医科大学
- 授与年月日
- 2021-03-16
- 授与年月日(W3CDTF)
- 2021-03-16
- 報告番号
- 甲第854号
- 学位
- 博士(医学)
- 博論授与番号
- 甲第854号
- 本文の言語コード
- eng
- 対象利用者
- 一般
- 一般注記
- doctoral医学系研究科Background: Viral respiratory tract infections, such as influenza A virus (IAV), are common and life-threatening illnesses worldwide. The mechanisms by which viruses are removed from the respiratory tract are indispensable for airway host defense. Mucociliary clearance is an airway defense mechanism that removes pathogens from the respiratory tract. The coordination and modulation of the ciliary beating of airway epithelial cells play key roles in maintaining effective mucociliary clearance. However, the impact of respiratory virus infection on ciliary activity and mucociliary clearance remains unclear.Methods: Tracheal samples were taken from wild-type (WT) and Toll-like receptor 3 (TLR3)-knockout (KO) mice. Transient organ culture of murine trachea was performed in the presence or absence of IAV, polyI:C, a synthetic TLR3 ligand, and/or reagents. Subsequently, cilia-driven flow and ciliary motility were analyzed. To evaluate cilia-driven flow, red fluorescent beads were loaded into culture media and movements of the beads onto the tracheal surface were observed using a fluorescence microscope. To evaluate ciliary motility, cilia tips were labeled with Indian ink diluted with culture medium. The motility of ink-labeled cilia tips was recorded by high-speed cameras.Results: Short-term IAV infection significantly increased cilia-driven flow and ciliary beat frequency (CBF) compared with the control level in WT culture. Whereas IAV infection did not elicit any increases of cilia-driven flow and CBF in TLR3-KO culture, indicating that TLR3 was essential to elicit an increase of cilia-driven flow and CBF in response to IAV infection. TLR3 activation by polyI:C readily induced adenosine triphosphate (ATP) release from the trachea and increases of cilia-driven flow and CBF in WT culture, but not in TLR3-KO culture. Moreover, blockade of purinergic P2 receptors (P2Rs) signaling using P2R antagonist, suramin, suppressed polyI:C-mediated increases of cilia-driven flow and CBF, indicating that TLR3-mediated ciliary activation depended on released extracellular ATP and the autocrine ATP-P2R loop.Conclusions: IAV infection readily increases ciliary activity and cilia-driven flow via TLR3 activation in the airway epithelium, thereby hastening mucociliary clearance and “sweeping” viruses from the airway as an initial host defense response. Mechanically, extracellular ATP release in response to TLR3 activation promotes ciliary activity through autocrine ATP-P2R loop.
- DOI
- info:doi/10.1186/s12931-020-01555-1
- 国立国会図書館永続的識別子
- info:ndljp/pid/11720315
- コレクション(共通)
- コレクション(障害者向け資料:レベル1)
- コレクション(個別)
- 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
- 収集根拠
- 博士論文(自動収集)
- 受理日(W3CDTF)
- 2021-09-06T03:11:00+09:00
- 作成日(W3CDTF)
- 2021-07-19
- 記録形式(IMT)
- application/pdf
- オンライン閲覧公開範囲
- 国立国会図書館内限定公開
- デジタル化資料送信
- 図書館・個人送信対象外
- 遠隔複写可否(NDL)
- 可
- 連携機関・データベース
- 国立国会図書館 : 国立国会図書館デジタルコレクション