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

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

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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  • Cytokines produced by the epithelium or by migrating inflammatory cells upon viral infection may affect cell-to-cell contact through interaction with TJs and desmosomes and thus disrupt the continuity of the epithelial barrier.

    “In addition, cytokines produced by the epithelium or by migrating inflammatory cells upon viral infection may affect cell-to-cell contact through interaction with TJs and desmosomes and thus disrupt the continuity of the epithelial barrier (135).”

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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
Venue
The Journal of Experimental Medicine
Published
2001-09-17
Volume
194
Issue
6
Pages
863-870
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
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
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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