Mycobacteria Target DC-SIGN to Suppress Dendritic Cell Function
Mycobacterium tuberculosis represents a world-wide health risk and immunosuppression is a particular problem in M. tuberculosis infections. Although macrophages are primarily infected, dendritic cells (DCs) are important in inducing cellular immune responses against M. tuberculosis. We hypothesized...
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| Format: | Online |
| Language: | English |
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The Rockefeller University Press
2003
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193797/ |
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pubmed-2193797 |
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pubmed-21937972008-04-11 Mycobacteria Target DC-SIGN to Suppress Dendritic Cell Function Geijtenbeek, Teunis B.H. van Vliet, Sandra J. Koppel, Estella A. Sanchez-Hernandez, Marta Vandenbroucke-Grauls, Christine M.J.E. Appelmelk, Ben van Kooyk, Yvette Article Mycobacterium tuberculosis represents a world-wide health risk and immunosuppression is a particular problem in M. tuberculosis infections. Although macrophages are primarily infected, dendritic cells (DCs) are important in inducing cellular immune responses against M. tuberculosis. We hypothesized that DCs represent a target for M. tuberculosis and that the observed immuno-suppression results from modulation of DC functions. We demonstrate that the DC-specific C-type lectin DC-SIGN is an important receptor on DCs that captures and internalizes intact Mycobacterium bovis bacillus Calmette-Guérin (BCG) through the mycobacterial cell wall component ManLAM. Antibodies against DC-SIGN block M. bovis BCG infection of DCs. ManLAM is also secreted by M. tuberculosis–infected macrophages and has been implicated as a virulence factor. Strikingly, ManLAM binding to DC-SIGN prevents mycobacteria- or LPS-induced DC maturation. Both mycobacteria and LPS induce DC maturation through Toll-like receptor (TLR) signaling, suggesting that DC-SIGN, upon binding of ManLAM, interferes with TLR-mediated signals. Blocking antibodies against DC-SIGN reverse the ManLAM-mediated immunosuppressive effects. Our results suggest that M. tuberculosis targets DC-SIGN both to infect DCs and to down-regulate DC-mediated immune responses. Moreover, we demonstrate that DC-SIGN has a broader pathogen recognition profile than previously shown, suggesting that DC-SIGN may represent a molecular target for clinical intervention in infections other than HIV-1. The Rockefeller University Press 2003-01-06 /pmc/articles/PMC2193797/ /pubmed/12515809 http://dx.doi.org/10.1084/jem.20021229 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Geijtenbeek, Teunis B.H. van Vliet, Sandra J. Koppel, Estella A. Sanchez-Hernandez, Marta Vandenbroucke-Grauls, Christine M.J.E. Appelmelk, Ben van Kooyk, Yvette |
| spellingShingle |
Geijtenbeek, Teunis B.H. van Vliet, Sandra J. Koppel, Estella A. Sanchez-Hernandez, Marta Vandenbroucke-Grauls, Christine M.J.E. Appelmelk, Ben van Kooyk, Yvette Mycobacteria Target DC-SIGN to Suppress Dendritic Cell Function |
| author_facet |
Geijtenbeek, Teunis B.H. van Vliet, Sandra J. Koppel, Estella A. Sanchez-Hernandez, Marta Vandenbroucke-Grauls, Christine M.J.E. Appelmelk, Ben van Kooyk, Yvette |
| author_sort |
Geijtenbeek, Teunis B.H. |
| title |
Mycobacteria Target DC-SIGN to Suppress Dendritic Cell Function |
| title_short |
Mycobacteria Target DC-SIGN to Suppress Dendritic Cell Function |
| title_full |
Mycobacteria Target DC-SIGN to Suppress Dendritic Cell Function |
| title_fullStr |
Mycobacteria Target DC-SIGN to Suppress Dendritic Cell Function |
| title_full_unstemmed |
Mycobacteria Target DC-SIGN to Suppress Dendritic Cell Function |
| title_sort |
mycobacteria target dc-sign to suppress dendritic cell function |
| description |
Mycobacterium tuberculosis represents a world-wide health risk and immunosuppression is a particular problem in M. tuberculosis infections. Although macrophages are primarily infected, dendritic cells (DCs) are important in inducing cellular immune responses against M. tuberculosis. We hypothesized that DCs represent a target for M. tuberculosis and that the observed immuno-suppression results from modulation of DC functions. We demonstrate that the DC-specific C-type lectin DC-SIGN is an important receptor on DCs that captures and internalizes intact Mycobacterium bovis bacillus Calmette-Guérin (BCG) through the mycobacterial cell wall component ManLAM. Antibodies against DC-SIGN block M. bovis BCG infection of DCs. ManLAM is also secreted by M. tuberculosis–infected macrophages and has been implicated as a virulence factor. Strikingly, ManLAM binding to DC-SIGN prevents mycobacteria- or LPS-induced DC maturation. Both mycobacteria and LPS induce DC maturation through Toll-like receptor (TLR) signaling, suggesting that DC-SIGN, upon binding of ManLAM, interferes with TLR-mediated signals. Blocking antibodies against DC-SIGN reverse the ManLAM-mediated immunosuppressive effects. Our results suggest that M. tuberculosis targets DC-SIGN both to infect DCs and to down-regulate DC-mediated immune responses. Moreover, we demonstrate that DC-SIGN has a broader pathogen recognition profile than previously shown, suggesting that DC-SIGN may represent a molecular target for clinical intervention in infections other than HIV-1. |
| publisher |
The Rockefeller University Press |
| publishDate |
2003 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193797/ |
| _version_ |
1611431308642222080 |