Loss of TLR2, TLR4, and TLR5 on Langerhans cells abolishes bacterial recognition.
It is unknown whether closely related epidermal dendritic cells, Langerhans cells (LCs), and dermal dendritic cells (DDCs) have unique functions. In this study, we show that human DDCs have a broad TLR expression profile, whereas human LCs have a selective impaired expression of cell surface TLR2, TLR4, and TLR5, all involved in bacterial recognition. This distinct TLR expression profile is acquired during the TGF-beta1-driven development of LCs in vitro. Consequently, and in contrast to DDCs, LCs weakly respond to bacterial TLR2, TLR4, and TLR5 ligands in terms of cytokine production and maturation, as well as to whole Gram-positive and Gram-negative bacteria, whereas their responsiveness to viral TLR ligands and viruses is fully active and comparable to DDCs. Unresponsiveness of LCs to bacteria may be a mechanism that contributes to tolerance to bacterial commensals that colonize the skin.
van der Aar
Angelic M G
AM
Department of Dermatology and.
Sylva-Steenland
Regien M R
RM
Bos
Jan D
JD
Kapsenberg
Martien L
ML
de Jong
Esther C
EC
Teunissen
Marcel B M
MB
D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006090:Gram-Negative Bacteria / Q000276:immunology*; D006094:Gram-Positive Bacteria / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000276:immunology*; D051198:Toll-Like Receptor 5 / Q000096:biosynthesis / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000494:pharmacology; D014780:Viruses / Q000276:immunology
C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D053773:Transforming Growth Factor beta1