PLoS Pathogens | |
HIV-1 gp120 Mannoses Induce Immunosuppressive Responses from Dendritic Cells | |
Meimei Shan1  Kaustuv Banerjee1  Robert Dionisio1  Dustin Charles1  Antu K Dey1  Lila Campbell-Gardener1  Per Johan Klasse1  John P Moore1  Rogier W Sanders2  Sai Prasad N Iyer3  William C Olson3  | |
[1] Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, United States of America;Laboratory of Experimental Virology, Department Medical Microbiology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands;Progenics Pharmaceuticals Incorporated, Tarrytown, New York, United States of America | |
关键词: T cells; HIV-1; Mannose; Immune response; Dendritic cells; Cytokines; Secretion; Cytotoxic T cells; | |
DOI : 10.1371/journal.ppat.0030169 | |
学科分类:生物科学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
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.
【 授权许可】
CC BY
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