Rapid influx and death of plasmacytoid dendritic cells in lymph nodes mediate depletion in acute simian immunodeficiency virus infection

PLoS Pathogens
Kevin N BrownSimon M Barratt-Boyes

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 producin...Continue Reading

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Citations

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Methods Mentioned

BETA
flow
flow cytometry
PCR
biopsy
density gradient centrifugation
FACS

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