Cargando…

Rapid Influx and Death of Plasmacytoid Dendritic Cells in Lymph Nodes Mediate Depletion in Acute Simian Immunodeficiency Virus Infection

Plasmacytoid dendritic cells (pDC) are essential innate immune system cells that are lost from the circulation in human immunodeficiency virus (HIV)–infected individuals associated with CD4(+) T cell decline and disease progression. pDC depletion is thought to be caused by migration to tissues or ce...

Descripción completa

Detalles Bibliográficos
Autores principales: Brown, Kevin N., Wijewardana, Viskam, Liu, Xiangdong, Barratt-Boyes, Simon M.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671605/
https://www.ncbi.nlm.nih.gov/pubmed/19424421
http://dx.doi.org/10.1371/journal.ppat.1000413
_version_ 1782166404927062016
author Brown, Kevin N.
Wijewardana, Viskam
Liu, Xiangdong
Barratt-Boyes, Simon M.
author_facet Brown, Kevin N.
Wijewardana, Viskam
Liu, Xiangdong
Barratt-Boyes, Simon M.
author_sort Brown, Kevin N.
collection PubMed
description Plasmacytoid dendritic cells (pDC) are essential innate immune system cells that are lost from the circulation in human immunodeficiency virus (HIV)–infected individuals associated with CD4(+) T cell decline and disease progression. pDC depletion is thought to be caused by migration to tissues or cell death, although few studies have addressed this directly. We used precise methods of enumeration and in vivo labeling with 5-bromo-2′-deoxyuridine to track recently divided pDC in blood and tissue compartments of monkeys with acute pathogenic simian immunodeficiency virus (SIV) infection. We show that pDC are lost from blood and peripheral lymph nodes within 14 days of infection, despite a normal frequency of pDC in bone marrow. Paradoxically, pDC loss masked a highly dynamic response characterized by rapid pDC mobilization into blood and a 10- to 20-fold increase in recruitment to lymph nodes relative to uninfected animals. Within lymph nodes, pDC had increased levels of apoptosis and necrosis, were uniformly activated, and were infected at frequencies similar to CD4(+) T cells. Nevertheless, remaining pDC had essentially normal functional responses to stimulation through Toll-like receptor 7, with half of lymph node pDC producing both TNF-α and IFN-α. These findings reveal that cell migration and death both contribute to pDC depletion in acute SIV infection. We propose that the rapid recruitment of pDC to inflamed lymph nodes in lentivirus infection has a pathologic consequence, bringing cells into close contact with virus, virus-infected cells, and pro-apoptotic factors leading to pDC death.
format Text
id pubmed-2671605
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-26716052009-05-08 Rapid Influx and Death of Plasmacytoid Dendritic Cells in Lymph Nodes Mediate Depletion in Acute Simian Immunodeficiency Virus Infection Brown, Kevin N. Wijewardana, Viskam Liu, Xiangdong Barratt-Boyes, Simon M. PLoS Pathog Research Article Plasmacytoid dendritic cells (pDC) are essential innate immune system cells that are lost from the circulation in human immunodeficiency virus (HIV)–infected individuals associated with CD4(+) T cell decline and disease progression. pDC depletion is thought to be caused by migration to tissues or cell death, although few studies have addressed this directly. We used precise methods of enumeration and in vivo labeling with 5-bromo-2′-deoxyuridine to track recently divided pDC in blood and tissue compartments of monkeys with acute pathogenic simian immunodeficiency virus (SIV) infection. We show that pDC are lost from blood and peripheral lymph nodes within 14 days of infection, despite a normal frequency of pDC in bone marrow. Paradoxically, pDC loss masked a highly dynamic response characterized by rapid pDC mobilization into blood and a 10- to 20-fold increase in recruitment to lymph nodes relative to uninfected animals. Within lymph nodes, pDC had increased levels of apoptosis and necrosis, were uniformly activated, and were infected at frequencies similar to CD4(+) T cells. Nevertheless, remaining pDC had essentially normal functional responses to stimulation through Toll-like receptor 7, with half of lymph node pDC producing both TNF-α and IFN-α. These findings reveal that cell migration and death both contribute to pDC depletion in acute SIV infection. We propose that the rapid recruitment of pDC to inflamed lymph nodes in lentivirus infection has a pathologic consequence, bringing cells into close contact with virus, virus-infected cells, and pro-apoptotic factors leading to pDC death. Public Library of Science 2009-05-08 /pmc/articles/PMC2671605/ /pubmed/19424421 http://dx.doi.org/10.1371/journal.ppat.1000413 Text en Brown 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.
spellingShingle Research Article
Brown, Kevin N.
Wijewardana, Viskam
Liu, Xiangdong
Barratt-Boyes, Simon M.
Rapid Influx and Death of Plasmacytoid Dendritic Cells in Lymph Nodes Mediate Depletion in Acute Simian Immunodeficiency Virus Infection
title Rapid Influx and Death of Plasmacytoid Dendritic Cells in Lymph Nodes Mediate Depletion in Acute Simian Immunodeficiency Virus Infection
title_full Rapid Influx and Death of Plasmacytoid Dendritic Cells in Lymph Nodes Mediate Depletion in Acute Simian Immunodeficiency Virus Infection
title_fullStr Rapid Influx and Death of Plasmacytoid Dendritic Cells in Lymph Nodes Mediate Depletion in Acute Simian Immunodeficiency Virus Infection
title_full_unstemmed Rapid Influx and Death of Plasmacytoid Dendritic Cells in Lymph Nodes Mediate Depletion in Acute Simian Immunodeficiency Virus Infection
title_short Rapid Influx and Death of Plasmacytoid Dendritic Cells in Lymph Nodes Mediate Depletion in Acute Simian Immunodeficiency Virus Infection
title_sort rapid influx and death of plasmacytoid dendritic cells in lymph nodes mediate depletion in acute simian immunodeficiency virus infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671605/
https://www.ncbi.nlm.nih.gov/pubmed/19424421
http://dx.doi.org/10.1371/journal.ppat.1000413
work_keys_str_mv AT brownkevinn rapidinfluxanddeathofplasmacytoiddendriticcellsinlymphnodesmediatedepletioninacutesimianimmunodeficiencyvirusinfection
AT wijewardanaviskam rapidinfluxanddeathofplasmacytoiddendriticcellsinlymphnodesmediatedepletioninacutesimianimmunodeficiencyvirusinfection
AT liuxiangdong rapidinfluxanddeathofplasmacytoiddendriticcellsinlymphnodesmediatedepletioninacutesimianimmunodeficiencyvirusinfection
AT barrattboyessimonm rapidinfluxanddeathofplasmacytoiddendriticcellsinlymphnodesmediatedepletioninacutesimianimmunodeficiencyvirusinfection