Article abstract
Nature Immunology 10, 1081 - 1088 (2009)
Published online: 30 August 2009 | doi:10.1038/ni.1778
Carbohydrate-specific signaling through the DC-SIGN signalosome tailors immunity to Mycobacterium tuberculosis, HIV-1 and Helicobacter pylori
Sonja I Gringhuis1,2, Jeroen den Dunnen2,3,4, Manja Litjens2,4, Michiel van der Vlist1,2 & Teunis B H Geijtenbeek1,2
Abstract
Cooperation between different innate signaling pathways induced by pattern-recognition receptors (PRRs) on dendritic cells (DCs) is crucial for tailoring adaptive immunity to pathogens. Here we show that carbohydrate-specific signaling through the C-type lectin DC-SIGN tailored cytokine production in response to distinct pathogens. DC-SIGN was constitutively associated with a signalosome complex consisting of the scaffold proteins LSP1, KSR1 and CNK and the kinase Raf-1. Mannose-expressing Mycobacterium tuberculosis and human immunodeficiency virus type 1 (HIV-1) induced the recruitment of effector proteins to the DC-SIGN signalosome to activate Raf-1, whereas fucose-expressing pathogens such as Helicobacter pylori actively dissociated the KSR1–CNK–Raf-1 complex from the DC-SIGN signalosome. This dynamic regulation of the signalosome by mannose- and fucose-expressing pathogens led to the enhancement or suppression of proinflammatory responses, respectively. Our study reveals another level of plasticity in tailoring adaptive immunity to pathogens.
- Center of Infection and Immunity Amsterdam and Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
- Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
- Present address: Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
- These authors contributed equally to this work.
Correspondence to: Sonja I Gringhuis1,2 e-mail: s.i.gringhuis@amc.uva.nl
Correspondence to: Teunis B H Geijtenbeek1,2 e-mail: t.b.geijtenbeek@amc.uva.nl
