title: Plasmacytoid dendritic cells infiltrate the skin in positive tuberculin skin test indurations.
abstract: Plasmacytoid dendritic cells (pDCs) are rarely present in normal skin but have been shown to infiltrate lesions of infections or autoimmune disorders. Here, we report that several DC subsets including CD123(+) BDCA-2/CD303(+) pDCs accumulate in the dermis in indurations induced by the tuberculin skin test (TST), used to screen immune sensitization by Mycobacterium tuberculosis. Although the purified protein derivate (PPD) used in the TST did not itself induce pDC recruitment or IFN-α production, the positive skin reactions showed high expression of the IFN-α-inducible protein MxA. In contrast, the local immune response to PPD was associated with substantial cell death and high expression of the cationic antimicrobial peptide LL37, which together can provide a means for pDC activation and IFN-α production. In vitro, pDCs showed low uptake of PPD compared with CD11c(+) and BDCA-3/CD141(+) myeloid DC subsets. Furthermore, supernatants from pDCs activated with LL37-DNA complexes reduced the high PPD uptake in myeloid DCs, as well as decreased their capacity to activate T-cell proliferation. Infiltrating pDCs in the TST reaction site may thus have a regulatory effect upon the antigen processing and presentation functions of surrounding potent myeloid DC subsets to limit potentially detrimental and excessive immune stimulation.
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Emily
authors.initials: E
authors.lastname: Bond
authors.forename: Frank
authors.initials: F
authors.lastname: Liang
authors.forename: Kerrie J
authors.initials: KJ
authors.lastname: Sandgren
authors.forename: Anna
authors.initials: A
authors.lastname: Smed-Sörensen
authors.forename: Peter
authors.initials: P
authors.lastname: Bergman
authors.forename: Susanna
authors.initials: S
authors.lastname: Brighenti
authors.forename: William C
authors.initials: WC
authors.lastname: Adams
authors.forename: Senait A
authors.initials: SA
authors.lastname: Betemariam
authors.forename: Molebogeng X
authors.initials: MX
authors.lastname: Rangaka
authors.forename: Christoph
authors.initials: C
authors.lastname: Lange
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
authors.forename: Jan
authors.initials: J
authors.lastname: Andersson
authors.forename: Karin
authors.initials: K
authors.lastname: Loré
mesh_terms: D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D054804:Cathelicidins / Q000235:genetics / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D064547:Myxovirus Resistance Proteins; D012867:Skin / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis / Q000276:immunology*
chemical_list: D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D054804:Cathelicidins; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D019204:GTP-Binding Proteins