{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:27:52Z","timestamp":1791350872227,"version":"4.3.1"},"reference-count":41,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,1,6]]},"abstract":"<jats:p>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-Gue\u0301rin (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\u2013infected 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.<\/jats:p>","DOI":"10.1084\/jem.20021229","type":"journal-article","created":{"date-parts":[[2003,1,6]],"date-time":"2003-01-06T14:02:37Z","timestamp":1041861757000},"page":"7-17","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":869,"title":["Mycobacteria Target DC-SIGN to Suppress Dendritic Cell Function"],"prefix":"10.1084","volume":"197","author":[{"given":"Teunis B.H.","family":"Geijtenbeek","sequence":"first","affiliation":[{"name":"1Department of Molecular Cell Biology, Vrije Universiteit Medical Center Amsterdam, 1081 BT Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra J.","family":"van Vliet","sequence":"additional","affiliation":[{"name":"1Department of Molecular Cell Biology, Vrije Universiteit Medical Center Amsterdam, 1081 BT Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estella A.","family":"Koppel","sequence":"additional","affiliation":[{"name":"1Department of Molecular Cell Biology, Vrije Universiteit Medical Center Amsterdam, 1081 BT Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Sanchez-Hernandez","sequence":"additional","affiliation":[{"name":"1Department of Molecular Cell Biology, Vrije Universiteit Medical Center Amsterdam, 1081 BT Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.J.E.","family":"Vandenbroucke-Grauls","sequence":"additional","affiliation":[{"name":"2Department of Medical Microbiology, Vrije Universiteit Medical Center Amsterdam, 1081 BT Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Appelmelk","sequence":"additional","affiliation":[{"name":"2Department of Medical Microbiology, Vrije Universiteit Medical Center Amsterdam, 1081 BT Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvette","family":"van Kooyk","sequence":"additional","affiliation":[{"name":"1Department of Molecular Cell Biology, Vrije Universiteit Medical Center Amsterdam, 1081 BT Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2002,12,23]]},"reference":[{"key":"2023072511523325400_BIB1","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1128\/iai.64.3.683-690.1996","volume":"64","year":"1996","journal-title":"Infect. 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