title: Recognition of Aspergillus fumigatus hyphae by human plasmacytoid dendritic cells is mediated by dectin-2 and results in formation of extracellular traps.
abstract: Plasmacytoid dendritic cells (pDCs) were initially considered as critical for innate immunity to viruses. However, our group has shown that pDCs bind to and inhibit the growth of Aspergillus fumigatus hyphae and that depletion of pDCs renders mice hypersusceptible to experimental aspergillosis. In this study, we examined pDC receptors contributing to hyphal recognition and downstream events in pDCs stimulated by A. fumigatus hyphae. Our data show that Dectin-2, but not Dectin-1, participates in A. fumigatus hyphal recognition, TNF-α and IFN-α release, and antifungal activity. Moreover, Dectin-2 acts in cooperation with the FcRγ chain to trigger signaling responses. In addition, using confocal and electron microscopy we demonstrated that the interaction between pDCs and A. fumigatus induced the formation of pDC extracellular traps (pETs) containing DNA and citrullinated histone H3. These structures closely resembled those of neutrophil extracellular traps (NETs). The microarray analysis of the pDC transcriptome upon A. fumigatus infection also demonstrated up-regulated expression of genes associated with apoptosis as well as type I interferon-induced genes. Thus, human pDCs directly recognize A. fumigatus hyphae via Dectin-2; this interaction results in cytokine release and antifungal activity. Moreover, hyphal stimulation of pDCs triggers a distinct pattern of pDC gene expression and leads to pET formation.
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America; Department of Immunology, Institute of Biomedical Sciences, São Paulo University, São Paulo, Brazil.
authors: Flávio V
authors: FV
authors: Loures
authors: Umeå Centre for Microbial Research, Laboratory for Molecular Infection Medicine Sweden (MIMS), Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
authors: Marc
authors: M
authors: Röhm
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors: Chrono K
authors: CK
authors: Lee
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors: Evelyn
authors: E
authors: Santos
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors: Jennifer P
authors: JP
authors: Wang
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors: Charles A
authors: CA
authors: Specht
authors: Department of Immunology, Institute of Biomedical Sciences, São Paulo University, São Paulo, Brazil.
authors: Vera L G
authors: VL
authors: Calich
authors: Umeå Centre for Microbial Research, Laboratory for Molecular Infection Medicine Sweden (MIMS), Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
authors: Constantin F
authors: CF
authors: Urban
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors: Stuart M
authors: SM
authors: Levitz
mesh_terms: D001228:Aspergillosis / Q000235:genetics / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D065206:Extracellular Traps / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D025301:Hyphae / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology*; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: C000593630:CLEC6A protein, human; D037181:Lectins, C-Type