Innate signaling by the C-type lectin DC-SIGN dictates immune responses.
Effective immune responses depend on the recognition of pathogens by dendritic cells (DCs) through pattern recognition receptors (PRRs). These receptors induce specific 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 particular, the C-type lectin DC-SIGN has emerged as a key player in the induction of immune responses against numerous pathogens by modulating TLR-induced activation. Recent reports have begun to elucidate the molecular mechanisms underlying these immune responses. Upon pathogen binding, DC-SIGN induces an intracellular signaling pathway 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-kappaB subunit p65, which induces specific gene transcription profiles. In addition, other DC-SIGN-ligands induce different 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.
den Dunnen
Jeroen
J
Department of Molecular Cell Biology and Immunology, VU University Medical Center, P.O. Box 7057, 1007 MC Amsterdam, The Netherlands.
Gringhuis
Sonja I
SI
Geijtenbeek
Teunis B H
TB
D000818:Animals; D001419:Bacteria / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation / Q000276:immunology; D019908:Proto-Oncogene Proteins c-raf / Q000276:immunology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D012471:Salivary Proteins and Peptides / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D016207:Cytokines; D037181:Lectins, C-Type; D016328:NF-kappa B; D019908:Proto-Oncogene Proteins c-raf; D011956:Receptors, Cell Surface; D012471:Salivary Proteins and Peptides; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C464566:Salp15 protein, Ixodes scapularis