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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2007
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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) |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
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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 |
work_keys_str_mv |
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