In this section
@inproceedings{Jha:2016,
author = {Jha, A and Progatzky, F and Wane, M and Thwaites, RS and McBrien, M and Brimley, J and Tunstall, T and Shattock, RJ and Bugeon, L and Openshaw, PJM and Dallman, MJ and Hansel, TT},
title = {Human nasal mucosal responses to TLR agonists are mirrored by the zebrafish gill},
year = {2016}
}
TY - CPAPER
AB - Introduction: There are few reliable ways to study respiratory mucosal immune responses to viruses, viral-type toll-like receptor (TLR) agonists and vaccines. To investigate innate immune responses to TLR agonists (TLR3: poly IC/ poly ICLC; TLR7/8: resiquimod), we compared the effects on human nasal mucosa and zebrafish gills in vivo. Methods: Nasal challenge of adult volunteers was performed with saline, poly IC (n=4), poly ICLC (n=4) or resiquimod (n=8; 5 non-atopic, 3 atopic). Nasal mucosal lining fluid (MLF) was obtained by nasosorption at regular intervals up to 24 hours after challenge; nasal obstruction was monitored by peak nasal inspiratory flow (PNIF) and total nasal symptom scores (TNSS). Cytokines and interferons were measured in MLF using electrochemiluminescence on the Meso Scale Discovery (MSD) platform. Adult zebrafish gills were exposed to the same TLR agonists and gene expression was quantified in gill tissue at similar time-points. Results: Nasal challenge with TLR3 agonists failed to elicit any significant responses when compared to saline. In contrast resiquimod (10μg/100μl per nostril) caused a potent induction of cytokines with an early release (1-3 hours) of IFN-α2a, TNF-α and IL-1β and a later release (after 4 hours) of IFN-γ. The 3 volunteers with the highest levels of IFN-α2a were atopic. Six volunteers were asymptomatic and two volunteers had flu-like symptoms. There were no significant changes in clinical correlates of nasal obstruction. After resiquimod administration, but not TLR3 agonists, zebrafish gills showed an immune profile remarkably analogous to human nasal responses. Conclusion: The TLR7/8 agonist resiquimod is a potent mucosal inducer of IFN-α2a, IFN-γ and proinflammatory cytokines, whilst TLR3 agonists failed to stimulate mucosal innate immune responses. Zebrafish gills accurately mimic human nasal mucosal responses following exposure to TLR agonists, offering translational app
AU - Jha,A
AU - Progatzky,F
AU - Wane,M
AU - Thwaites,RS
AU - McBrien,M
AU - Brimley,J
AU - Tunstall,T
AU - Shattock,RJ
AU - Bugeon,L
AU - Openshaw,PJM
AU - Dallman,MJ
AU - Hansel,TT
PY - 2016///
TI - Human nasal mucosal responses to TLR agonists are mirrored by the zebrafish gill
ER -