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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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Detection of TLR mRNA by RT-PCR in freshly isolated monocytes, CD11c+ imDCs, and plasmacytoid pre-DCs. The three cell populations were isolated by cell sorting to the purity of >99%. cDNAs were amplified for 35 cycles and were separated on a 3% agarose gel containing ethidium bromide. The data shown are representative of three experiments.
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Figure 1: Detection of TLR mRNA by RT-PCR in freshly isolated monocytes, CD11c+ imDCs, and plasmacytoid pre-DCs. The three cell populations were isolated by cell sorting to the purity of >99%. cDNAs were amplified for 35 cycles and were separated on a 3% agarose gel containing ethidium bromide. The data shown are representative of three experiments.

Mentions: Three populations of cells, monocytes, CD11c+ imDCs, and plasmacytoid pre-DCs, were isolated by cell sorting, to a purity >99%. As shown in Fig. 1, monocytes expressed high levels of TLR 1, 2, 4, 5, and 8, low level of TLR6, and undetectable levels of TLR 3, 7, 9, or 10 by RT-PCR. CD11c+ imDCs expressed high levels of TLR 1, 2, and 3, low levels of TLR 5, 6, 8, and 10, and undetectable levels of TLR 4, 7, and 9. In marked contrast to monocytes and CD11c+ imDCs, plasmacytoid pre-DCs express high levels of TLR 7 and 9 (Fig. 1). They also expressed low levels of TLR 1, 6, and 10, but not TLR 2, 3, 4, 5, or 8. Thus, monocytes and CD11c+ imDCs, and plasmacytoid pre-DCs express distinct sets of TLRs.


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)

Detection of TLR mRNA by RT-PCR in freshly isolated monocytes, CD11c+ imDCs, and plasmacytoid pre-DCs. The three cell populations were isolated by cell sorting to the purity of >99%. cDNAs were amplified for 35 cycles and were separated on a 3% agarose gel containing ethidium bromide. The data shown are representative of three experiments.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Detection of TLR mRNA by RT-PCR in freshly isolated monocytes, CD11c+ imDCs, and plasmacytoid pre-DCs. The three cell populations were isolated by cell sorting to the purity of >99%. cDNAs were amplified for 35 cycles and were separated on a 3% agarose gel containing ethidium bromide. The data shown are representative of three experiments.
Mentions: Three populations of cells, monocytes, CD11c+ imDCs, and plasmacytoid pre-DCs, were isolated by cell sorting, to a purity >99%. As shown in Fig. 1, monocytes expressed high levels of TLR 1, 2, 4, 5, and 8, low level of TLR6, and undetectable levels of TLR 3, 7, 9, or 10 by RT-PCR. CD11c+ imDCs expressed high levels of TLR 1, 2, and 3, low levels of TLR 5, 6, 8, and 10, and undetectable levels of TLR 4, 7, and 9. In marked contrast to monocytes and CD11c+ imDCs, plasmacytoid pre-DCs express high levels of TLR 7 and 9 (Fig. 1). They also expressed low levels of TLR 1, 6, and 10, but not TLR 2, 3, 4, 5, or 8. Thus, monocytes and CD11c+ imDCs, and plasmacytoid pre-DCs express distinct sets of TLRs.

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