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Volume 9 Supplement 2

AIDS Vaccine 2012

  • Poster presentation
  • Open Access

HIV-1 gp120 impairs the induction of B cell responses by TLR9-activated plasmacytoid dendritic cells

  • 1,
  • 1,
  • 1 and
  • 1
Retrovirology20129 (Suppl 2) :P9

https://doi.org/10.1186/1742-4690-9-S2-P9

  • Published:

Keywords

  • TLR9 Ligand
  • TLR9 Agonist
  • Plasmacytoid Dendritic Cell
  • Protein Vaccine
  • Plasma Cell Differentiation

Background

Plasmacytoid dendritic cells (pDCs) play a central role in innate and adaptive immunity to viral infections, including HIV-1. pDCs produce substantial quantities of type I IFN and proinflammatory cytokines upon stimulation by Toll-like receptors (TLR), specifically TLR7 or TLR9. We have studied how gp120 affects human pDC responses to TLR9 agonists, and the subsequent ability of the pDCs to stimulate B cells, with the goal of learning how better to induce B cell responses to Env protein vaccines.

Methods

pDCs were isolated from human peripheral blood using CD304 magnetic beads, and then treated with endotoxin-free recombinant gp120 during stimulation with TLR9 agonists. IFN-α, IL-6, TNF-α, IRF-7 and BAFF were quantified at the protein or mRNA level. Co-cultures were performed to study how gp120-treatment of the pDCs affected their abilities to stimulate B cell responses, specifically proliferation, differentiation to plasma cells and IgG/IgM production.

Results

We found that gp120 impaired IFN-α production by pDCs in response to TLR9 (CpG-ODN), but not TLR7, stimulation. Receptor-blocking studies showed the inhibitory effects were mediated via CD4 and the C-type lectin receptor BDCA-2, but not via CCR5 or CXCR4. Treatment with gp120 inhibited CpG-induced pDC maturation, TNF-α and IL-6 production and IRF-7 and BAFF mRNA expression. The gp120-treated, CpG-activated pDCs also had impaired abilities to induce B cell proliferation, plasma cell differentiation and Ig production, due at least in part to decreased expression of BAFF and other cytokines.

Conclusion

Taken together, our data show that HIV-1 gp120 impairs pDC functions and B cell activation, and imply that TLR9 ligands may not be good adjuvants to use in combination with Env-based vaccines.

Authors’ Affiliations

(1)
Weill Cornell Medical College, New York, NY, USA

Copyright

© Chung et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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