eprintid: 13128
rev_number: 29
userid: 677
importid: 461
dir: disk0/00/01/31/28
datestamp: 2012-07-25 14:20:29
lastmod: 2021-06-12 21:55:19
status_changed: 2012-07-25 14:20:29
type: article
metadata_visibility: show
contact_email: smbb@pitt.edu
item_issues_count: 0
eprint_status: archive
creators_name: Brown, KN
creators_name: Wijewardana, V
creators_name: Liu, X
creators_name: Barratt-Boyes, SM
contributors_type: http://www.loc.gov/loc.terms/relators/EDT
contributors_name: Douek, Danny C.
title: Rapid influx and death of plasmacytoid dendritic cells in lymph nodes mediate depletion in acute simian immunodeficiency virus infection
ispublished: pub
divisions: sch_gsph_infectiousdiseasesmicrobiology
full_text_status: public
abstract: 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. © 2009 Brown et al.
date: 2009-05-01
date_type: published
publication: PLoS Pathogens
volume: 5
number: 5
refereed: TRUE
issn: 1553-7366
centers: cen_other_vaccineresearch
id_number: 10.1371/journal.ppat.1000413
pmcid: PMC2671605
pmid: 19424421
citation:   Brown, KN and Wijewardana, V and Liu, X and Barratt-Boyes, SM  (2009) Rapid influx and death of plasmacytoid dendritic cells in lymph nodes mediate depletion in acute simian immunodeficiency virus infection.  PLoS Pathogens, 5 (5).   ISSN 1553-7366     
document_url: http://d-scholarship-dev.library.pitt.edu/13128/1/Rapid_Influx.pdf
document_url: http://d-scholarship-dev.library.pitt.edu/13128/8/licence.txt