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The Journal of Immunology, 2006, 177: 298-305.
Copyright © 2006 by The American Association of Immunologists

TLR Activation of Langerhans Cell-Like Dendritic Cells Triggers an Antiviral Immune Response1

Claudia N. Renn*, David Jesse Sanchez{dagger}, Maria Teresa Ochoa*, Annaliza J. Legaspi*, Chang-Keun Oh{ddagger}, Philip T. Liu*, Stephan R. Krutzik*, Peter A. Sieling*, Genhong Cheng{dagger} and Robert L. Modlin2,*,{dagger}

* Division of Dermatology and {dagger} Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angles (UCLA), Los Angeles, CA 90095; and {ddagger} Department of Dermatology, College of Medicine, Pusan National University Hospital, Pusan, Korea

Langerhans cells (LC) are a unique subset of dendritic cells (DC), present in the epidermis and serving as the first line of defense against pathogens invading the skin. To investigate the role of human LCs in innate immune responses, we examined TLR expression and function of LC-like DCs derived from CD34+ progenitor cells and compared them to DCs derived from peripheral blood monocytes (monocyte-derived DC; Mo-DC). LC-like DCs and Mo-DCs expressed TLR1–10 mRNAs at comparable levels. Although many of the TLR-induced cytokine patterns were similar between the two cell types, stimulation with the TLR3 agonist poly(I:C) triggered significantly higher amounts of the IFN-inducible chemokines CXCL9 (monokine induced by IFN-{gamma}) and CXCL11 (IFN-{gamma}-inducible T cell {alpha} chemoattractant) in LC-like DCs as compared with Mo-DCs. Supernatants from TLR3-activated LC-like DCs reduced intracellular replication of vesicular stomatitis virus in a type I IFN-dependent manner. Finally, CXCL9 colocalized with LCs in skin biopsy specimens from viral infections. Together, our data suggest that LCs exhibit a direct antiviral activity that is dependent on type I IFN as part of the innate immune system.




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