Human Langerhans Cells Express a Specific TLR Profile and Differentially Respond to Viruses and Gram-Positive Bacteria

Dendritic cells (DC) are APCs essential for the development of primary immune responses. In pluristratified epithelia, Langerhans cells (LC) are a critical subset of DC which take up Ags and migrate toward lymph nodes upon inflammatory stimuli. TLR allow detection of pathogen-associated molecular pa...

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Bibliographic Details
Published in:Journal of Immunology 2006-12, Vol.177 (11), p.7959-7967
Main Authors: Flacher, Vincent, Bouschbacher, Marielle, Verronese, Estelle, Massacrier, Catherine, Sisirak, Vanja, Berthier-Vergnes, Odile, de Saint-Vis, Blandine, Caux, Christophe, Dezutter-Dambuyant, Colette, Lebecque, Serge, Valladeau, Jenny
Format: Article
Language:English
Subjects:
Cellular Biology
Gram-Positive Bacteria
Gram-Positive Bacteria - immunology
Humans
Interleukin-6
Interleukin-6 - immunology
Interleukin-6 - metabolism
Interleukin-8
Interleukin-8 - immunology
Interleukin-8 - metabolism
Langerhans Cells
Langerhans Cells - immunology
Langerhans Cells - metabolism
Life Sciences
Reverse Transcriptase Polymerase Chain Reaction
RNA, Double-Stranded
RNA, Double-Stranded - immunology
RNA, Double-Stranded - metabolism
Skin
Skin - cytology
Skin - immunology
Toll-Like Receptors
Toll-Like Receptors - agonists
Toll-Like Receptors - immunology
Toll-Like Receptors - metabolism
Tumor Necrosis Factor-alpha
Tumor Necrosis Factor-alpha - immunology
Tumor Necrosis Factor-alpha - metabolism
Viruses
Viruses - immunology
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Summary:Dendritic cells (DC) are APCs essential for the development of primary immune responses. In pluristratified epithelia, Langerhans cells (LC) are a critical subset of DC which take up Ags and migrate toward lymph nodes upon inflammatory stimuli. TLR allow detection of pathogen-associated molecular patterns (PAMP) by different DC subsets. The repertoire of TLR expressed by human LC is uncharacterized and their ability to directly respond to PAMP has not been systematically investigated. In this study, we show for the first time that freshly purified LC from human skin express mRNA encoding TLR1, TLR2, TLR3, TLR5, TLR6 and TLR10. In addition, keratinocytes ex vivo display TLR1-5, TLR7, and TLR10. Accordingly, highly enriched immature LC efficiently respond to TLR2 agonists peptidoglycan and lipoteichoic acid from Gram-positive bacteria, and to dsRNA which engages TLR3. In contrast, LC do not directly sense TLR7/8 ligands and LPS from Gram-negative bacteria, which signals through TLR4. TLR engagement also results in cytokine production, with marked differences depending on the PAMP detected. TLR2 and TLR3 ligands increase IL-6 and IL-8 production, while dsRNA alone stimulates TNF-alpha release. Strikingly, only peptidoglycan triggers IL-10 secretion, thereby suggesting a specific function in tolerance to commensal Gram-positive bacteria. However, LC do not produce IL-12p70 or type I IFNs. In conclusion, human LC are equipped with TLR that enable direct detection of PAMP from viruses and Gram-positive bacteria, subsequent phenotypic maturation, and differential cytokine production. This implies a significant role for LC in the control of skin immune responses.
ISSN:0022-1767
1550-6606
1365-2567
DOI:10.4049/jimmunol.177.11.7959