Cited by 1,964Immune Response and InflammationImmunotherapy and Immune ResponsesImmune responses and vaccinations

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Subsets of Human Dendritic Cell Precursors Express Different Toll-like Receptors and Respond to Different Microbial Antigens

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Kadowaki, Norimitsu, Ho, Stephen, Antonenko, Svetlana, de Waal Malefyt, Rene, Kastelein, Robert A., Bazan, Fernando, Liu, Yong-Jun·2001·The Journal of Experimental Medicine

DOI 10.1084/jem.194.6.863PMC PMC2195968

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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)-α 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-α. CD11c+ imDCs preferentially express TLR 1, 2, and 3 and respond to TLR 2-ligand PGN by producing large amounts of TNF-α, and to viral double-stranded RNA-like molecule poly I:C, by producing IFN-α 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.

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Authors: Kadowaki, N., Ho, S., Antonenko, S., de Waal Malefyt, R., Kastelein, R. A., Bazan, F., & Liu, Y.-J.
Affiliations: aDNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304
ORCID: Kadowaki, Norimitsu
Liu, Yong-Jun
Venue: The Journal of Experimental Medicine
Publisher: Rockefeller University Press
Published: 2001-09-17
Volume: 194
Issue: 6
Pages: 863-870
ISSN: 0022-1007 (ISSN-L)
1540-9538
DOI: 10.1084/jem.194.6.863
PMC: PMC2195968
OpenAlex: W2104904748
Cited by: 1,964
References: 45
Citations by year: 2026: 10 · 2025: 12 · 2024: 16 · 2023: 16 · 2022: 27 · 2021: 37 · 2020: 39 · 2019: 38 · 2018: 28 · 2017: 62 · 2016: 52 · 2015: 56 · 2014: 86 · 2013: 90 · 2012: 95
FWCI: 40.14
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: The Journal of Experimental Medicine (publishedVersion)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords: Toll-like receptors, dendritic cell precursors, plasmacytoid dendritic cells, monocytes, TLR2, TLR4, TLR7, TLR9, peptidoglycan, lipoteichoic acid, lipopolysaccharide, CpG oligodeoxynucleotides, poly(I:C), TNF-α, interleukin-6, interferon-alpha, IL-12, dendritic cell development
MeSH terms: Dendritic Cells, Hematopoietic Stem Cells, Humans, Lipopolysaccharides, Membrane Glycoproteins, Monocytes, Oligodeoxyribonucleotides, Receptors, Cell Surface, Staphylococcus aureus, Biomarkers, Gene Expression, Cytokines, Drosophila Proteins, Toll-Like Receptors, Toll-Like Receptor 1, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptor 7, Toll-Like Receptor 9

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Subsets of Human Dendritic Cell Precursors Express Different Toll-like Receptors and Respond to Different Microbial Antigens

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