HIV-1 gp120 mannoses induce immunosuppressive responses from dendritic cells Academic Article uri icon

Overview

MeSH Major

  • Dendritic Cells
  • HIV Envelope Protein gp120
  • Lectins, C-Type
  • Mannose

abstract

  • The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 is a vaccine immunogen that can signal via several cell surface receptors. To investigate whether receptor biology could influence immune responses to gp120, we studied its interaction with human, monocyte-derived dendritic cells (MDDCs) in vitro. Gp120 from the HIV-1 strain JR-FL induced IL-10 expression in MDDCs from 62% of donors, via a mannose C-type lectin receptor(s) (MCLR). Gp120 from the strain LAI was also an IL-10 inducer, but gp120 from the strain KNH1144 was not. The mannose-binding protein cyanovirin-N, the 2G12 mAb to a mannose-dependent gp120 epitope, and MCLR-specific mAbs inhibited IL-10 expression, as did enzymatic removal of gp120 mannose moieties, whereas inhibitors of signaling via CD4, CCR5, or CXCR4 were ineffective. Gp120-stimulated IL-10 production correlated with DC-SIGN expression on the cells, and involved the ERK signaling pathway. Gp120-treated MDDCs also responded poorly to maturation stimuli by up-regulating activation markers inefficiently and stimulating allogeneic T cell proliferation only weakly. These adverse reactions to gp120 were MCLR-dependent but independent of IL-10 production. Since such mechanisms might suppress immune responses to Env-containing vaccines, demannosylation may be a way to improve the immunogenicity of gp120 or gp140 proteins.

publication date

  • November 2007

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2048530

Digital Object Identifier (DOI)

  • 10.1371/journal.ppat.0030169

PubMed ID

  • 17983270

Additional Document Info

start page

  • e169

volume

  • 3

number

  • 11