HIV-1 gp120 impairs the induction of B cell responses by TLR9-activated plasmacytoid dendritic cells. Academic Article uri icon

Overview

MeSH

  • Antigens, CD4
  • B-Cell Activating Factor
  • Cell Communication
  • Coculture Techniques
  • Gene Expression
  • Humans
  • Interferon Regulatory Factor-7
  • Interferon-alpha
  • Interleukin-6
  • Lymphocyte Activation
  • Primary Cell Culture
  • Recombinant Proteins
  • Signal Transduction
  • Toll-Like Receptor 7

MeSH Major

  • B-Lymphocytes
  • Dendritic Cells
  • HIV Envelope Protein gp120
  • HIV-1
  • Oligodeoxyribonucleotides
  • Toll-Like Receptor 9

abstract

  • Plasmacytoid dendritic cells (pDCs) play a central role in innate and adaptive immune responses to viral infections, including HIV type 1 (HIV-1). pDCs produce substantial quantities of type I IFN and proinflammatory cytokines upon stimulation via TLRs, specifically TLR7 or TLR9. The HIV-1 envelope glycoproteins, exemplified by the gp120 monomer, are the focus of vaccines aimed at inducing B cell responses. We have studied how the interactions of gp120 with various receptors on human pDCs affect the activation of these cells via TLR9 and their subsequent ability to stimulate B cells. We observed that IFN-α production by pDCs in response to TLR9, but not TLR7, stimulation was reduced by exposure to gp120. Specifically, gp120 inhibited the CpG-induced maturation of pDCs and their expression of TNF-α, IL-6, TLR9, IFN regulatory factor 7, and BAFF. Receptor-blocking and cross-linking studies showed that these inhibitory effects of gp120 were mediated by interactions with CD4 and mannose-binding C-type lectin receptors, but not with the chemokine receptors CCR5 and CXCR4. Of note is that gp120 inhibited the activation of B cells by TLR9-stimulated pDCs. Taken together, our data show that HIV-1 gp120 impairs pDC functions, including activation of B cell responses, and imply that TLR9 ligands may not be good adjuvants to use in combination with envelope glycoprotein vaccines.

publication date

  • December 1, 2012

has subject area

  • Antigens, CD4
  • B-Cell Activating Factor
  • B-Lymphocytes
  • Cell Communication
  • Coculture Techniques
  • Dendritic Cells
  • Gene Expression
  • HIV Envelope Protein gp120
  • HIV-1
  • Humans
  • Interferon Regulatory Factor-7
  • Interferon-alpha
  • Interleukin-6
  • Lymphocyte Activation
  • Oligodeoxyribonucleotides
  • Primary Cell Culture
  • Recombinant Proteins
  • Signal Transduction
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3504132

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1201905

PubMed ID

  • 23100517

Additional Document Info

start page

  • 5257

end page

  • 5265

volume

  • 189

number

  • 11