Carbohydrate-specific signaling through the DC-SIGN signalosome tailors immunity to Mycobacterium tuberculosis, HIV-1 and Helicobacter pylori

SI Gringhuis, J Den Dunnen, M Litjens… - Nature …, 2009 - nature.com
SI Gringhuis, J Den Dunnen, M Litjens, M Van Der Vlist, TBH Geijtenbeek
Nature immunology, 2009nature.com
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 …
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.
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