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PLoS Pathog. 2015 Feb 6;11(2):e1004643. doi: 10.1371/journal.ppat.1004643. eCollection 2015 Feb.

Recognition of Aspergillus fumigatus hyphae by human plasmacytoid dendritic cells is mediated by dectin-2 and results in formation of extracellular traps.

Author information

1
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.
2
Umeå Centre for Microbial Research, Laboratory for Molecular Infection Medicine Sweden (MIMS), Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
3
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
4
Department of Immunology, Institute of Biomedical Sciences, São Paulo University, São Paulo, Brazil.

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.

PMID:
25659141
PMCID:
PMC4450068
DOI:
10.1371/journal.ppat.1004643
[Indexed for MEDLINE]
Free PMC Article

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