UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

2-6-2015

Document Type

Article

Disciplines

Immunity | Immunopathology

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-alpha and IFN-alpha release, and antifungal activity. Moreover, Dectin-2 acts in cooperation with the FcRgamma 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.

Rights and Permissions

Citation: PLoS Pathog. 2015 Feb 6;11(2):e1004643. doi: 10.1371/journal.ppat.1004643. Link to article on publisher's site

DOI of Published Version

10.1371/journal.ppat.1004643

Comments

Copyright: © 2015 Loures et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Related Resources

Link to Article in PubMed

Keywords

Aspergillus fumigatus, Gene expression, Antifungals, Cytokines, Gene regulation, Histones, Microarrays, Apoptosis

Journal/Book/Conference Title

PLoS pathogens

PubMed ID

25659141

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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