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Influenza A virus enhances ciliary activity and mucociliary clearance via TLR3 in airway epithelium

Authors :
Tetsuro Suzuki
Yosuke Kamiya
Hironao Hozumi
Masato Karayama
Kazuki Furuhashi
Masahiko Ito
Takafumi Suda
Naoki Inui
Noriyuki Enomoto
Tomoyuki Fujisawa
Koji Ikegami
Yuzo Suzuki
Yutaro Nakamura
Hideki Yasui
Mineo Katsumata
Mitsutoshi Setou
Source :
Respiratory Research, Vol 21, Iss 1, Pp 1-13 (2020), Respiratory Research
Publication Year :
2020
Publisher :
BMC, 2020.

Abstract

BackgroundViral 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.MethodsTracheal 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.ResultsShort-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.ConclusionsIAV 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.

Details

Language :
English
Volume :
21
Issue :
1
Database :
OpenAIRE
Journal :
Respiratory Research
Accession number :
edsair.doi.dedup.....b225578313290fa4d73a9a117222d2e8
Full Text :
https://doi.org/10.1186/s12931-020-01555-1