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

By N. Kadowaki, S. Ho, S. Antonenko, R. de Waal Malefyt, R. Kastelein, F. Bazan, Yong‐jun Liu. Journal of Experimental Medicine, 2001

2,235 citations recorded by the source corpus.

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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/4be02739eda0f24b835b154c8e190392dc8d114c

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In Immunology

Citations in the corpus

Immune surveillance in the skin: mechanisms and clinical consequences (2004, background): “TLR expression is variable and might identify subsets of innate immune cells, such as DCs, with specific function”
Dendritic cells as therapeutic vaccines against cancer (2005, background): “For example, TLR9 (a receptor for demethylated DNA) is expressed only by pDCs, whereas myeloid DCs preferentially express TLR2 and TLR4 (receptors for the bacterial products peptidoglycan and LPS, respectively”
Endocytosis of HIV-1 activates plasmacytoid dendritic cells via Toll-like receptor-viral RNA interactions. (2005, positive): “They differ in other aspects, including differential expression of C-type lectin receptors (CLRs) and TLRs. Studies have demonstrated that TLR7 mRNA is expressed by both blood-derived pDCs and MDCs, whereas TLR8 mRNA is restricted to MDCs (2–6).”
Photodynamic therapy and anti-tumour immunity (2006, background): “So far, 13 TLR family members have been identified on monocytes and macrophages, dendritic cells, mast cells and some epithelial cell”
Small anti-viral compounds activate immune cells via the TLR7 MyD88–dependent signaling pathway (2002, background): “Of the ten TLR family members, only pDC2s express TLR7 and TLR”
Role of Toll-Like Receptors in Pathogen Recognition (2003, background): “TLR7 B cells, plasmacytoid precursor DC (24, 32) Highly induced by IL-6, moderately by other cytokines (86)”
Immune sensing of DNA (2013, neutral): “It will also be important to more fully understand the cell biology of DNA sensing, particularly as it relates to STING function, and to determine which chaperone and sorting adaptor proteins are required to direct correct signaling responses (Kagan, 2012).”