Slc15a4, a Gene Required for pDC Sensing of TLR Ligands, Is Required to Control Persistent Viral Infection

Plasmacytoid dendritic cells (pDCs) are the major producers of type I IFN in response to viral infection and have been shown to direct both innate and adaptive immune responses in vitro. However, in vivo evidence for their role in viral infection is lacking. We evaluated the contribution of pDCs to...

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Main Authors: Blasius, Amanda L., Krebs, Philippe, Sullivan, Brian M., Oldstone, Michael B., Popkin, Daniel L.
Format: Online
Language:English
Published: Public Library of Science 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3441671/
id pubmed-3441671
recordtype oai_dc
spelling pubmed-34416712012-10-01 Slc15a4, a Gene Required for pDC Sensing of TLR Ligands, Is Required to Control Persistent Viral Infection Blasius, Amanda L. Krebs, Philippe Sullivan, Brian M. Oldstone, Michael B. Popkin, Daniel L. Research Article Plasmacytoid dendritic cells (pDCs) are the major producers of type I IFN in response to viral infection and have been shown to direct both innate and adaptive immune responses in vitro. However, in vivo evidence for their role in viral infection is lacking. We evaluated the contribution of pDCs to acute and chronic virus infection using the feeble mouse model of pDC functional deficiency. We have previously demonstrated that feeble mice have a defect in TLR ligand sensing. Although pDCs were found to influence early cytokine secretion, they were not required for control of viremia in the acute phase of the infection. However, T cell priming was deficient in the absence of functional pDCs and the virus-specific immune response was hampered. Ultimately, infection persisted in feeble mice. We conclude that pDCs are likely required for efficient T cell priming and subsequent viral clearance. Our data suggest that reduced pDC functionality may lead to chronic infection. Public Library of Science 2012-09-13 /pmc/articles/PMC3441671/ /pubmed/23028315 http://dx.doi.org/10.1371/journal.ppat.1002915 Text en © 2012 Blasius et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Blasius, Amanda L.
Krebs, Philippe
Sullivan, Brian M.
Oldstone, Michael B.
Popkin, Daniel L.
spellingShingle Blasius, Amanda L.
Krebs, Philippe
Sullivan, Brian M.
Oldstone, Michael B.
Popkin, Daniel L.
Slc15a4, a Gene Required for pDC Sensing of TLR Ligands, Is Required to Control Persistent Viral Infection
author_facet Blasius, Amanda L.
Krebs, Philippe
Sullivan, Brian M.
Oldstone, Michael B.
Popkin, Daniel L.
author_sort Blasius, Amanda L.
title Slc15a4, a Gene Required for pDC Sensing of TLR Ligands, Is Required to Control Persistent Viral Infection
title_short Slc15a4, a Gene Required for pDC Sensing of TLR Ligands, Is Required to Control Persistent Viral Infection
title_full Slc15a4, a Gene Required for pDC Sensing of TLR Ligands, Is Required to Control Persistent Viral Infection
title_fullStr Slc15a4, a Gene Required for pDC Sensing of TLR Ligands, Is Required to Control Persistent Viral Infection
title_full_unstemmed Slc15a4, a Gene Required for pDC Sensing of TLR Ligands, Is Required to Control Persistent Viral Infection
title_sort slc15a4, a gene required for pdc sensing of tlr ligands, is required to control persistent viral infection
description Plasmacytoid dendritic cells (pDCs) are the major producers of type I IFN in response to viral infection and have been shown to direct both innate and adaptive immune responses in vitro. However, in vivo evidence for their role in viral infection is lacking. We evaluated the contribution of pDCs to acute and chronic virus infection using the feeble mouse model of pDC functional deficiency. We have previously demonstrated that feeble mice have a defect in TLR ligand sensing. Although pDCs were found to influence early cytokine secretion, they were not required for control of viremia in the acute phase of the infection. However, T cell priming was deficient in the absence of functional pDCs and the virus-specific immune response was hampered. Ultimately, infection persisted in feeble mice. We conclude that pDCs are likely required for efficient T cell priming and subsequent viral clearance. Our data suggest that reduced pDC functionality may lead to chronic infection.
publisher Public Library of Science
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3441671/
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