TLR activation of Langerhans cell-like dendritic cells triggers an antiviral immune response.
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.
Renn
Claudia N
CN
Division of Dermatology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Sanchez
David Jesse
DJ
Ochoa
Maria Teresa
MT
Legaspi
Annaliza J
AJ
Oh
Chang-Keun
CK
Liu
Philip T
PT
Krutzik
Stephan R
SR
Sieling
Peter A
PA
Cheng
Genhong
G
Modlin
Robert L
RL
D002460:Cell Line; D002478:Cells, Cultured; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D004817:Epidermis / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006801:Humans; D007370:Interferon Type I / Q000502:physiology; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D008024:Ligands; D008976:Molluscum Contagiosum / Q000276:immunology / Q000821:virology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D014860:Warts / Q000276:immunology / Q000821:virology
C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D007370:Interferon Type I; D008024:Ligands; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3