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The Journal of Immunology, 2007, 178: 1986-1990.
Copyright © 2007 by The American Association of Immunologists, Inc.


CUTTING EDGE

Cutting Edge: Loss of TLR2, TLR4, and TLR5 on Langerhans Cells Abolishes Bacterial Recognition1

Angelic M.G. van der Aar*, Regien M. R. Sylva-Steenland*, Jan D. Bos*, Martien L. Kapsenberg*,{dagger}, Esther C. de Jong2,{dagger} and Marcel B. M. Teunissen2,3,*

* Department of Dermatology and {dagger} Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by the Netherlands Institute for Pigment Disorders.

2 E.C.d.J. and M.B.M.T. contributed equally to this work.

3 Address correspondence and reprint requests to Dr. Marcel B. M. Teunissen, Department of Dermatology, University of Amsterdam, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands. E-mail address: m.b.teunissen{at}amc.uva.nl

4 Abbreviations used in this paper: DC, dendritic cell; LC, Langerhans cell; DDC, dermal DC; PRR, pattern recognition receptor; moDC, monocyte-derived DC; moLC, monocyte-derived LC; PGN, peptidoglycan; FLU, influenza virus.




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