CD14 is a coreceptor of Toll-like receptors 7 and 9

Autor: Melanie Planyavsky, Sylvia Knapp, Omar Sharif, Christoph Baumann, Keiryn L. Bennett, Florian Grebien, Giulio Superti-Furga, Andreas Pichlmair, Stephan Blüml, Manuela Bruckner, Pawel Pasierbek, Karin Aumayr, Jacques Colinge, Irene M. Aspalter
Rok vydání: 2010
Předmět:
Proteomics
Molecular Sequence Data
Immunology
Lipopolysaccharide Receptors
chemical and pharmacologic phenomena
Endosomes
Biology
Article
Proinflammatory cytokine
Mice
03 medical and health sciences
0302 clinical medicine
immune system diseases
parasitic diseases
Animals
Humans
Immunology and Allergy
Receptor
Cells
Cultured
030304 developmental biology
0303 health sciences
Toll-like receptor
Imiquimod
Membrane Glycoproteins
Innate immune system
Base Sequence
Interleukin-6
virus diseases
hemic and immune systems
TLR7
biology.organism_classification
Molecular biology
3. Good health
Cell biology
Mice
Inbred C57BL
Oligodeoxyribonucleotides
Toll-Like Receptor 7
Influenza A virus
Vesicular stomatitis virus
Toll-Like Receptor 9
Aminoquinolines
Nucleic acid
Female
Signal transduction
030215 immunology
Zdroj: The Journal of Experimental Medicine
ISSN: 1540-9538
0022-1007
DOI: 10.1084/jem.20101111
Popis: CD14 interacts with and is essential for the functions of endosomal TLR7 and TLR9 in mice.
Recognition of pathogens by the innate immune system requires proteins that detect conserved molecular patterns. Nucleic acids are recognized by cytoplasmic sensors as well as by endosomal Toll-like receptors (TLRs). It has become evident that TLRs require additional proteins to be activated by their respective ligands. In this study, we show that CD14 (cluster of differentiation 14) constitutively interacts with the MyD88-dependent TLR7 and TLR9. CD14 was necessary for TLR7- and TLR9-dependent induction of proinflammatory cytokines in vitro and for TLR9-dependent innate immune responses in mice. CD14 associated with TLR9 stimulatory DNA in precipitation experiments and confocal imaging. The absence of CD14 led to reduced nucleic acid uptake in macrophages. Additionally, CD14 played a role in the stimulation of TLRs by viruses. Using various types of vesicular stomatitis virus, we showed that CD14 is dispensable for viral uptake but is required for the triggering of TLR-dependent cytokine responses. These data show that CD14 has a dual role in nucleic acid–mediated TLR activation: it promotes the selective uptake of nucleic acids, and it acts as a coreceptor for endosomal TLR activation.
Databáze: OpenAIRE
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