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J Immunol. 2012 Dec 1;189(11):5257-65. doi: 10.4049/jimmunol.1201905. Epub 2012 Oct 24.

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

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  • 1Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021, USA.

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.

PMID:
23100517
[PubMed - indexed for MEDLINE]
PMCID:
PMC3504132
Free PMC Article

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