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2009Innate signaling by the C-type lectin DC-SIGN dictates immune.pdf

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2009Innate signaling by the C-type lectin DC-SIGN dictates immune

Cancer Immunol Immunother (2009) 58:1149–1157 DOI 10.1007/s00262-008-0615-1 SYMPOSIUM PAPER Innate signaling by the C-type lectin DC-SIGN dictates immune responses Jeroen den Dunnen · Sonja I. Gringhuis · Teunis B. H. Geijtenbeek Received: 5 August 2008 / Accepted: 13 October 2008 / Published online: 8 November 2008 ? The Author(s) 2008. This article is published with open access at S Abstract EVective immune responses depend on the rec- ognition of pathogens by dendritic cells (DCs) through pat- tern recognition receptors (PRRs). These receptors induce speciWc signaling pathways that lead to the induction of immune responses against the pathogens. It is becoming evident that C-type lectins are also important PRRs. In par- ticular, the C-type lectin DC-SIGN has emerged as a key player in the induction of immune responses against numer- ous pathogens by modulating TLR-induced activation. Recent reports have begun to elucidate the molecular mech- anisms underlying these immune responses. Upon pathogen binding, DC-SIGN induces an intracellular signaling path- way with a central role for the serine/threonine kinase Raf-1. For several pathogens that interact with DC-SIGN, including Mycobacterium tuberculosis and HIV-1, Raf-1 activation leads to acetylation of NF-B subunit p65, which induces speciWc gene transcription proWles. In addition, other DC-SIGN-ligands induce diVerent signaling pathways downstream of Raf-1, indicating that DC-SIGN-signaling is tailored to the pathogen. In this review we will discuss in detail the current knowledge about DC-SIGN signaling and its implications on immunity. Keywords C-type lectin · DC-SIGN · HIV-1 · Innate signaling · Mycobacteria · Raf-1 Introduction EVective immune responses depend on the recognition of pathogens by dendritic cells (DCs) through pattern recog- nition receptors (PRRs) [23]. These PRRs recognize so- called pattern associated molecular patterns (PAMPs), which are conserved groups of molecules from pathogens tha