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dc.contributor.authorLoures, Flavio V.
dc.contributor.authorRohm, Marc
dc.contributor.authorLee, Chrono K.
dc.contributor.authorSantos, Evelyn
dc.contributor.authorWang, Jennifer P.
dc.contributor.authorSpecht, Charles A.
dc.contributor.authorCalich, Vera L.G.
dc.contributor.authorUrban, Constantin F.
dc.contributor.authorLevitz, Stuart M.
dc.date2022-08-11T08:09:41.000
dc.date.accessioned2022-08-23T16:40:26Z
dc.date.available2022-08-23T16:40:26Z
dc.date.issued2015-02-06
dc.date.submitted2015-04-27
dc.identifier.citationPLoS Pathog. 2015 Feb 6;11(2):e1004643. doi: 10.1371/journal.ppat.1004643. <a href="http://dx.doi.org/10.1371/journal.ppat.1004643">Link to article on publisher's site</a>
dc.identifier.issn1553-7366 (Linking)
dc.identifier.doi10.1371/journal.ppat.1004643
dc.identifier.pmid25659141
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39682
dc.description.abstractPlasmacytoid 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=25659141&dopt=Abstract">Link to Article in PubMed</a>
dc.rights<p>Copyright: © 2015 Loures et al. This is an open access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited</p>
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAspergillus fumigatus
dc.subjectGene expression
dc.subjectAntifungals
dc.subjectCytokines
dc.subjectGene regulation
dc.subjectHistones
dc.subjectMicroarrays
dc.subjectApoptosis
dc.subjectImmunity
dc.subjectImmunopathology
dc.titleRecognition of Aspergillus fumigatus hyphae by human plasmacytoid dendritic cells is mediated by dectin-2 and results in formation of extracellular traps
dc.typeJournal Article
dc.source.journaltitlePLoS pathogens
dc.source.volume11
dc.source.issue2
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3482&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2479
dc.identifier.contextkey7036617
refterms.dateFOA2022-08-23T16:40:26Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/2479
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.source.pagese1004643


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<p>Copyright: © 2015 Loures et al. This is an open access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited</p>
Except where otherwise noted, this item's license is described as <p>Copyright: © 2015 Loures et al. This is an open access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited</p>