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

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...

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Autores principales: Meimei Shan, Per Johan Klasse, Kaustuv Banerjee, Antu K Dey, Sai Prasad N Iyer, Robert Dionisio, Dustin Charles, Lila Campbell-Gardener, William C Olson, Rogier W Sanders, John P Moore
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Publicado: Public Library of Science (PLoS) 2007
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Acceso en línea:https://doaj.org/article/c4960ccf37e145a796aa35e5d170473a
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spelling oai:doaj.org-article:c4960ccf37e145a796aa35e5d170473a2021-11-25T05:46:20ZHIV-1 gp120 mannoses induce immunosuppressive responses from dendritic cells.1553-73661553-737410.1371/journal.ppat.0030169https://doaj.org/article/c4960ccf37e145a796aa35e5d170473a2007-11-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.0030169https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The 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.Meimei ShanPer Johan KlasseKaustuv BanerjeeAntu K DeySai Prasad N IyerRobert DionisioDustin CharlesLila Campbell-GardenerWilliam C OlsonRogier W SandersJohn P MoorePublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 3, Iss 11, p e169 (2007)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Meimei Shan
Per Johan Klasse
Kaustuv Banerjee
Antu K Dey
Sai Prasad N Iyer
Robert Dionisio
Dustin Charles
Lila Campbell-Gardener
William C Olson
Rogier W Sanders
John P Moore
HIV-1 gp120 mannoses induce immunosuppressive responses from dendritic cells.
description 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.
format article
author Meimei Shan
Per Johan Klasse
Kaustuv Banerjee
Antu K Dey
Sai Prasad N Iyer
Robert Dionisio
Dustin Charles
Lila Campbell-Gardener
William C Olson
Rogier W Sanders
John P Moore
author_facet Meimei Shan
Per Johan Klasse
Kaustuv Banerjee
Antu K Dey
Sai Prasad N Iyer
Robert Dionisio
Dustin Charles
Lila Campbell-Gardener
William C Olson
Rogier W Sanders
John P Moore
author_sort Meimei Shan
title HIV-1 gp120 mannoses induce immunosuppressive responses from dendritic cells.
title_short HIV-1 gp120 mannoses induce immunosuppressive responses from dendritic cells.
title_full HIV-1 gp120 mannoses induce immunosuppressive responses from dendritic cells.
title_fullStr HIV-1 gp120 mannoses induce immunosuppressive responses from dendritic cells.
title_full_unstemmed HIV-1 gp120 mannoses induce immunosuppressive responses from dendritic cells.
title_sort hiv-1 gp120 mannoses induce immunosuppressive responses from dendritic cells.
publisher Public Library of Science (PLoS)
publishDate 2007
url https://doaj.org/article/c4960ccf37e145a796aa35e5d170473a
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