HIV-1 gp120 mannoses induce immunosuppressive responses from dendritic cells.

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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Shan M,Klasse PJ,Banerjee K,Dey AK,Iyer SP,Dionisio R,Charles D,Campbell-Gardener L,Olson WC,Sanders RW,Moore JP

doi

10.1371/journal.ppat.0030169

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

e169

issue

11

eissn

1553-7366

issn

1553-7374

pii

07-PLPA-RA-0438

journal_volume

3

pub_type

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