TLR7 and TLR8 activate distinct pathways in monocytes during RNA virus infection
File(s)
Accepted version
Author(s)
de Marcken, Marine
Dhaliwal, Khushwant
Danielsen, Ann Caroline
Gautron, Anne Sophie
Dominguez-Villar, Margarita
Type
Journal Article
Abstract
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.
Date Issued
2019-10-29
Date Acceptance
2019-09-19
Citation
Science Signaling, 2019, 12 (605), pp.1-18
ISSN
1945-0877
Publisher
American Association for the Advancement of Science (AAAS)
Start Page
1
End Page
18
Journal / Book Title
Science Signaling
Volume
12
Issue
605
Copyright Statement
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works http://www.sciencemag.org/about/science-licenses-journal-article-reuseThis is an article distributed under the terms of the Science Journals Default License.
Identifier
https://stke.sciencemag.org/content/12/605/eaaw1347
Subjects
0601 Biochemistry and Cell Biology
Publication Status
Published
Date Publish Online
2019-10-29