The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Human Langerhans Cells Express a Specific TLR Profile and Differentially Respond to Viruses and Gram-Positive Bacteria
Open accessAbstract
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-α 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.
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Cites
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Immunobiology of Dendritic Cells
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Self-citationToll-like receptor control of the adaptive immune responses
Iwasaki, A., & Medzhitov, R. (2004) · Nature Immunology · doi:10.1038/ni1112 · Cited by 4,193
The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5
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Innate immune recognition of viral infection
Kawai, T., & Akira, S. (2006) · Nature Immunology · doi:10.1038/ni1303 · Cited by 1,899
Peptidoglycan- and Lipoteichoic Acid-induced Cell Activation Is Mediated by Toll-like Receptor 2
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Endotoxin-tolerant Mice Have Mutations in Toll-like Receptor 4 (Tlr4)
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Cutting Edge: Role of Toll-Like Receptor 1 in Mediating Immune Response to Microbial Lipoproteins
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Nicolas, J.-F., & Guy, B. (2008) · Expert Review of Vaccines · doi:10.1586/14760584.7.8.1201 · Cited by 259
Jurkin, J., Schichl, Y. M., Koeffel, R., Bauer, T., Richter, S., Konradi, S., Gesslbauer, B., & Strobl, H. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903021 · Cited by 139
YAO, C., OH, J.-H., LEE, D. H., BAE, J.-S., JIN, C. L., PARK, C.-H., & CHUNG, J. H. (2015) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2015.2146 · Cited by 90
Epidermal Langerhans cells – changing views on their function in vivo
Romani, N., Ebner, S., Tripp, C. H., Flacher, V., Koch, F., & Stoitzner, P. (2006) · Immunology Letters · doi:10.1016/j.imlet.2006.05.010 · Cited by 81
Self-citationIwamoto, K., Nümm, T. J., Koch, S., Herrmann, N., Leib, N., & Bieber, T. (2018) · Allergy · doi:10.1111/all.13460 · Cited by 61
Metadata
- Authors
- Flacher, V., Bouschbacher, M., Verronèse, E., Massacrier, C., Sisirak, V., Berthier-Vergnes, O., de Saint-Vis, B., Caux, C., Dezutter-Dambuyant, C., Lebecque, S., & Valladeau, J.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-12-01
- Volume
- 177
- Issue
- 11
- Pages
- 7959-7967
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1904661552
- Cited by
- 268
- References
- 52
- FWCI
- 7.79
- Type
- journal article
- Language
- en
- Open access
- green
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- Flacher, V., Bouschbacher, M., Verronèse, E., Massacrier, C., Sisirak, V., Berthier-Vergnes, O., de Saint-Vis, B., Caux, C., Dezutter-Dambuyant, C., Lebecque, S., & Valladeau, J. (2006). Human Langerhans Cells Express a Specific TLR Profile and Differentially Respond to Viruses and Gram-Positive Bacteria. The Journal of Immunology. https://doi.org/10.4049/jimmunol.177.11.7959
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