Symposium Paper

Cancer Immunology, Immunotherapy

, Volume 58, Issue 7, pp 1149-1157

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

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

  • Jeroen den DunnenAffiliated withDepartment of Molecular Cell Biology and Immunology, VU University Medical Center
  • , Sonja I. GringhuisAffiliated withDepartment of Molecular Cell Biology and Immunology, VU University Medical Center
  • , Teunis B. H. GeijtenbeekAffiliated withDepartment of Molecular Cell Biology and Immunology, VU University Medical Center Email author 

Abstract

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-κB 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.

Keywords

C-type lectin DC-SIGN HIV-1 Innate signaling Mycobacteria Raf-1