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PMID: 11561001 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens.

The Journal of experimental medicine ·Vol. 194 ·No. 6 ·2001-09-17 ·Pages 863-9

Kadowaki N, Ho S, Antonenko S, Malefyt RW, Kastelein RA, Bazan F, Liu YJ

Abstract

Toll-like receptors (TLRs) are ancient microbial pattern recognition receptors highly conserved from Drosophila to humans. To investigate if subsets of human dendritic cell precursors (pre-DC), including monocytes (pre-DC1), plasmacytoid DC precursors (pre-DC2), and CD11c(+) immature DCs (imDCs) are developed to recognize different microbes or microbial antigens, we studied their TLR expression and responses to microbial antigens. We demonstrate that whereas monocytes preferentially express TLR 1, 2, 4, 5, and 8, plasmacytoid pre-DC strongly express TLR 7 and 9. In accordance with these TLR expression profiles, monocytes respond to the known microbial ligands for TLR2 (peptidoglycan [PGN], lipoteichoic acid) and TLR4 (lipopolysaccharide), by producing tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. In contrast, plasmacytoid pre-DCs only respond to the microbial TLR9-ligand, CpG-ODNs (oligodeoxynucleotides [ODNs] containing unmethylated CpG motifs), by producing IFN-alpha. CD11c(+) imDCs preferentially express TLR 1, 2, and 3 and respond to TLR 2-ligand PGN by producing large amounts of TNF-alpha, and to viral double-stranded RNA-like molecule poly I:C, by producing IFN-alpha and IL-12. The expression of distinct sets of TLRs and the corresponding difference in reactivity to microbial molecules among subsets of pre-DCs and imDCs support the concept that they have developed through distinct evolutionary pathways to recognize different microbial antigens.

MeSH Terms
Biomarkers Cytokines/biosynthesis Dendritic Cells/cytology,drug effects,immunology,metabolism Drosophila Proteins Gene Expression Hematopoietic Stem Cells/cytology,drug effects,immunology,metabolism Humans Lipopolysaccharides/immunology,pharmacology Membrane Glycoproteins/genetics Monocytes/cytology,metabolism Oligodeoxyribonucleotides/immunology Receptors, Cell Surface/genetics Staphylococcus aureus/immunology Toll-Like Receptor 1 Toll-Like Receptor 2 Toll-Like Receptor 4 Toll-Like Receptor 7 Toll-Like Receptor 9 Toll-Like Receptors
Chemicals
Biomarkers CPG-oligonucleotide Cytokines Drosophila Proteins Lipopolysaccharides Membrane Glycoproteins Oligodeoxyribonucleotides Receptors, Cell Surface TLR2 protein, human TLR4 protein, human TLR7 protein, human TLR9 protein, human Toll-Like Receptor 1 Toll-Like Receptor 2 Toll-Like Receptor 4 Toll-Like Receptor 7 Toll-Like Receptor 9 Toll-Like Receptors
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Kadowaki N
DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA.
Ho S
Antonenko S
Malefyt R W
Kastelein R A
Bazan F
Liu Y J
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.194.6.863
Published
2001-09-17
Pages
863-9
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2195968
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.194.6.863 PMC Full Text View journal details
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