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Mycobacteria target DC-SIGN to suppress dendritic cell function
Teunis B H Geijtenbeek1, Sandra J Van Vliet, Estella A Koppel
1Department of Molecular Cell Biology, Vrije Universiteit Medical Center Amsterdam, 1081 BT Amsterdam, Netherlands. T.Geijtenbeek.Cell@med.vu.nl
The Journal of Experimental Medicine
|January 8, 2003
Summary
Mycobacterium tuberculosis uses DC-SIGN on dendritic cells (DCs) to infect them and suppress immune responses. Targeting DC-SIGN could offer new treatments for tuberculosis and other infections.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Tuberculosis (TB) poses a global health threat, with immunosuppression complicating infections.
- Dendritic cells (DCs) are crucial for initiating cellular immunity against Mycobacterium tuberculosis, despite macrophages being the primary infected cell type.
Purpose of the Study:
- To investigate if Mycobacterium tuberculosis targets DCs and modulates their function to cause immunosuppression.
- To explore the role of DC-specific C-type lectin DC-SIGN in Mycobacterium tuberculosis infection and immune evasion.
Main Methods:
- Utilized antibodies against DC-SIGN to block Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection of DCs.
- Investigated the interaction between ManLAM, a mycobacterial cell wall component, and DC-SIGN.
- Assessed the impact of ManLAM-DC-SIGN binding on DC maturation induced by mycobacteria or lipopolysaccharide (LPS) via Toll-like receptor (TLR) signaling.
Main Results:
- DC-SIGN acts as a key receptor for the uptake of intact Mycobacterium bovis BCG by DCs, mediated by ManLAM.
- ManLAM binding to DC-SIGN inhibits DC maturation, interfering with TLR-mediated signaling pathways.
- Blocking DC-SIGN with antibodies reversed the immunosuppressive effects of ManLAM and prevented DC infection.
Conclusions:
- Mycobacterium tuberculosis exploits DC-SIGN for both DC infection and the suppression of DC-mediated immune responses.
- DC-SIGN exhibits a broader pathogen recognition capability than previously understood, indicating its potential as a therapeutic target for various infections, including but not limited to HIV-1.