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

Kadowaki N, Ho S, Antonenko S, Malefyt RW, Kastelein RA, Bazan F, Liu YJ - J. Exp. Med. (2001)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA.

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.

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TNF-α, IL-6, IFN-α, and IL-12 production by monocytes (Mono), CD11c+ imDCs, and plasmacytoid pre-DCs (pDC) stimulated with microbial molecules that trigger different TLR signaling. The three cell populations were cultured with 10 μg/ml PGN, 10 μg/ml LTA, 10 μg/ml LPS, 50 μg/ml poly I:C, or with 5 μM CpG-ODN AAC-30 for 24 h, and the concentrations of cytokines in the supernatants were measured by ELISA. The data shown are representative of four or five experiments.
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Figure 3: TNF-α, IL-6, IFN-α, and IL-12 production by monocytes (Mono), CD11c+ imDCs, and plasmacytoid pre-DCs (pDC) stimulated with microbial molecules that trigger different TLR signaling. The three cell populations were cultured with 10 μg/ml PGN, 10 μg/ml LTA, 10 μg/ml LPS, 50 μg/ml poly I:C, or with 5 μM CpG-ODN AAC-30 for 24 h, and the concentrations of cytokines in the supernatants were measured by ELISA. The data shown are representative of four or five experiments.

Mentions: As shown in Fig. 3, the TLR2-ligand, PGN, stimulated monocytes to produce large amounts of TNF-α and IL-6. PGNs stimulate CD11c+ imDCs to produce large amounts of TNF-α, and small amounts of IL-6 and IL-12. PGN did not stimulate plasmacytoid pre-DCs to produce any of the cytokines tested. Plasmacytoid pre-DCs died in cultures either with medium or with PGN (data not shown). Similar to PGN, the other TLR2-ligand, LTA, stimulated monocytes to produce large amounts of TNF-α and IL-6. However, unlike PGN, LTA did not stimulate CD11c+ imDCs to produce detectable levels of cytokines tested. Plasmacytoid pre-DCs did not respond to LTA.


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

Kadowaki N, Ho S, Antonenko S, Malefyt RW, Kastelein RA, Bazan F, Liu YJ - J. Exp. Med. (2001)

TNF-α, IL-6, IFN-α, and IL-12 production by monocytes (Mono), CD11c+ imDCs, and plasmacytoid pre-DCs (pDC) stimulated with microbial molecules that trigger different TLR signaling. The three cell populations were cultured with 10 μg/ml PGN, 10 μg/ml LTA, 10 μg/ml LPS, 50 μg/ml poly I:C, or with 5 μM CpG-ODN AAC-30 for 24 h, and the concentrations of cytokines in the supernatants were measured by ELISA. The data shown are representative of four or five experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195968&req=5

Figure 3: TNF-α, IL-6, IFN-α, and IL-12 production by monocytes (Mono), CD11c+ imDCs, and plasmacytoid pre-DCs (pDC) stimulated with microbial molecules that trigger different TLR signaling. The three cell populations were cultured with 10 μg/ml PGN, 10 μg/ml LTA, 10 μg/ml LPS, 50 μg/ml poly I:C, or with 5 μM CpG-ODN AAC-30 for 24 h, and the concentrations of cytokines in the supernatants were measured by ELISA. The data shown are representative of four or five experiments.
Mentions: As shown in Fig. 3, the TLR2-ligand, PGN, stimulated monocytes to produce large amounts of TNF-α and IL-6. PGNs stimulate CD11c+ imDCs to produce large amounts of TNF-α, and small amounts of IL-6 and IL-12. PGN did not stimulate plasmacytoid pre-DCs to produce any of the cytokines tested. Plasmacytoid pre-DCs died in cultures either with medium or with PGN (data not shown). Similar to PGN, the other TLR2-ligand, LTA, stimulated monocytes to produce large amounts of TNF-α and IL-6. However, unlike PGN, LTA did not stimulate CD11c+ imDCs to produce detectable levels of cytokines tested. Plasmacytoid pre-DCs did not respond to LTA.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA.

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.

Show MeSH
Related in: MedlinePlus