Imperial College London
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DrMargaritaDominguez-Villar

Faculty of Medicine, Department of Infectious Disease

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 3735m.dominguez-villar Website

 
 
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Location

 

117Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{de:2019:10.1126/scisignal.aaw1347,
author = {de, Marcken M and Dhaliwal, K and Danielsen, AC and Gautron, AS and Dominguez-Villar, M},
doi = {10.1126/scisignal.aaw1347},
journal = {Science Signaling},
pages = {1--18},
title = {TLR7 and TLR8 activate distinct pathways in monocytes during RNA virus infection},
url = {http://dx.doi.org/10.1126/scisignal.aaw1347},
volume = {12},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Human blood CD14+ monocytes are bone marrow–derived white blood cells that sense and respond to pathogens. Although innate immune activation by RNA viruses preferentially occurs through intracellular RIG-I–like receptors, other nucleic acid recognition receptors, such as Toll-like receptors (TLRs), play a role in finely programming the final outcome of virus infection. Here, we dissected how human monocytes respond to infection with either Coxsackie (CV), encephalomyocarditis (EMCV), influenza A (IAV), measles (MV), Sendai (SV), or vesicular stomatitis (VSV) virus. We found that in monocytes, type I interferon (IFN) and cytokine responses to infection were RNA virus specific and differentially involved TLR7 and TLR8, which sense single-stranded RNA. These TLRs activated distinct signaling cascades in monocytes, which correlated with differences in the production of cytokines involved in the polarization of CD4+ T helper cells. Furthermore, we found that TLR7 signaling specifically increased expression of the transcription factor FOSL1, which reduced IL-27 and TNFα production by monocytes. TLR7, but not TLR8, activation of monocytes also stimulated Ca2+ flux that prevented type I IFN responses. Our work demonstrates that in human monocytes, TLR7 and TLR8 triggered different signaling pathways that contribute to distinct phenotypes during RNA virus infection. In addition, we defined individual targets within these pathways that promoted specific T helper and antiviral responses.
AU  - de,Marcken M
AU  - Dhaliwal,K
AU  - Danielsen,AC
AU  - Gautron,AS
AU  - Dominguez-Villar,M
DO  - 10.1126/scisignal.aaw1347
EP  - 18
PY  - 2019///
SN  - 1945-0877
SP  - 1
TI  - TLR7 and TLR8 activate distinct pathways in monocytes during RNA virus infection
T2  - Science Signaling
UR  - http://dx.doi.org/10.1126/scisignal.aaw1347
UR  - https://stke.sciencemag.org/content/12/605/eaaw1347
UR  - http://hdl.handle.net/10044/1/74468
VL  - 12
ER  -
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