RT Journal Article
SR Electronic
T1 Characterization of toll-like receptor 7 (TLR7) expression on airway nerves
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA914
DO 10.1183/13993003.congress-2015.PA914
VO 46
IS suppl 59
A1 Matthew Drake
A1 Katherine Lebold
A1 Emily Blum
A1 Allison Fryer
A1 David Jacoby
YR 2015
UL http://erj.ersjournals.com/content/46/suppl_59/PA914.abstract
AB Background: TLR7 detects viral single-stranded RNA and triggers an antiviral immune response. We have shown TLR7 agonists acutely relax human and murine airways through nitric oxide production.Objective: To characterize TLR7 expression and signaling pathways in the lung.Methods: Whole mount murine lungs and deceased-donor human trachea and esophagi were immunofluorescently labeled with antibodies against TLR7, neuronal nitric oxide synthase (nNOS) and the neuronal marker PGP9.5. Images were obtained with an LSM780 laser-scanning confocal microscope. TLR7 function was assessed in the airways of C57Bl/6 wild-type and MyD88 knockout mice in an organ bath. Airways contracted with methacholine (10 µM) were treated with TLR7 agonist R837 (10-300 µM). Some airways were treated with the transcriptional inhibitor actinomycin (10 µM).Results: TLR7 was expressed on subsets of airway nerves, but not airway smooth muscle. TLR7 was also expressed on esophageal nerves that project to the trachea, pleura and primary bronchi. nNOS colocalized with TLR7 staining on airway nerves and on the esophageal-tracheal nerve plexus. TLR7 agonist R837 dose-dependently relaxed pre-contracted wild-type and MyD88 knockout murine airways equally. TLR7 agonist-mediated relaxation was unaffected by treatment with actinomycin.Conclusions: Airway parasympathetic nerves and nerves originating in the esophagus coexpress TLR7 and nNOS. TLR7-expressing esophageal nerves may correspond to nitric oxide-producing nonadrenergic noncholinergic (NANC) nerves. Airway nerves are implicated as the source of TLR7-induced nitric oxide production.Funding Source: This project was supported by NIH grants HL121254, HL124165, HL113023, AR061567, ES017592.