Announcement

Collapse
No announcement yet.

TLR7 and TLR8 activate distinct pathways in monocytes during RNA virus infection

Collapse
X
 
  • Filter
  • Time
  • Show
Clear All
new posts

  • TLR7 and TLR8 activate distinct pathways in monocytes during RNA virus infection


    Sci Signal. 2019 Oct 29;12(605). pii: eaaw1347. doi: 10.1126/scisignal.aaw1347. TLR7 and TLR8 activate distinct pathways in monocytes during RNA virus infection.

    de Marcken M1, Dhaliwal K1, Danielsen AC1, Gautron AS1, Dominguez-Villar M2.
    Author information

    1 Department of Neurology, Yale School of Medicine, New Haven, CT 06520, USA. 2 Department of Neurology, Yale School of Medicine, New Haven, CT 06520, USA. m.dominguez-villar@imperial.ac.uk.

    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.
    Copyright ? 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.


    PMID: 31662487 DOI: 10.1126/scisignal.aaw1347

Working...
X