Modulation of Immune Signaling and Metabolism Highlights Host and Fungal Transcriptional Responses in Mouse Models of Invasive Pulmonary Aspergillosis

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dc.contributor.authorKale, Shiv D.en
dc.contributor.authorAyubi, Tariqen
dc.contributor.authorChung, Dawoonen
dc.contributor.authorTubau-Juni, Nuriaen
dc.contributor.authorLeber, Andrewen
dc.contributor.authorDang, Ha X.en
dc.contributor.authorKaryala, Saikumaren
dc.contributor.authorHontecillas, Raquelen
dc.contributor.authorLawrence, Christopher B.en
dc.contributor.authorCramer, Robert A.en
dc.contributor.authorBassaganya-Riera, Josepen
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.date.accessioned2019-01-02T15:41:29Zen
dc.date.available2019-01-02T15:41:29Zen
dc.date.issued2017-12-06en
dc.description.abstractIncidences of invasive pulmonary aspergillosis, an infection caused predominantly by Aspergillus fumigatus, have increased due to the growing number of immunocompromised individuals. While A. fumigatus is reliant upon deficiencies in the host to facilitate invasive disease, the distinct mechanisms that govern the host-pathogen interaction remain enigmatic, particularly in the context of distinct immune modulating therapies. To gain insights into these mechanisms, RNA-Seq technology was utilized to sequence RNA derived from lungs of 2 clinically relevant, but immunologically distinct murine models of IPA on days 2 and 3 post inoculation when infection is established and active disease present. Our findings identify notable differences in host gene expression between the chemotherapeutic and steroid models at the interface of immunity and metabolism. RT-qPCR verified model specific and nonspecific expression of 23 immune-associated genes. Deep sequencing facilitated identification of highly expressed fungal genes. We utilized sequence similarity and gene expression to categorize the A. fumigatus putative in vivo secretome. RT-qPCR suggests model specific gene expression for nine putative fungal secreted proteins. Our analysis identifies contrasting responses by the host and fungus from day 2 to 3 between the two models. These differences may help tailor the identification, development, and deployment of host-and/or fungal-targeted therapeutics.en
dc.description.notesA portion of this study was funded through internal funding from the Biocomplexity Institute of Virginia Tech to SDK. This study is also based upon work supported by the Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA), via the Army Research Office (ARO) under cooperative Agreement Number W911NF-17-2-0105. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of the ODNI, IARPA, ARO, or the U.S. Government. The efforts of Robert A Cramer were funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (R01 AI081838). RAC holds an Investigators in the Pathogenesis of Infectious Diseases Award from the Burroughs Wellcome Fund (BWF).en
dc.description.sponsorshipBiocomplexity Institute of Virginia Tech; Office of the Director of National Intelligence (ODNI); Intelligence Advanced Research Projects Activity (IARPA), via the Army Research Office (ARO) [W911NF-17-2-0105]; HHS \ NIH \ National Institute of Allergy and Infectious Diseases (NIAID) [R01 AI081838]; Burroughs Wellcome Fund (BWF)en
dc.format.extent25 pagesen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41598-017-17000-1en
dc.identifier.issn2045-2322en
dc.identifier.other17096en
dc.identifier.urihttp://hdl.handle.net/10919/86542en
dc.identifier.volume7en
dc.language.isoen_USen
dc.publisherSpringer Natureen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectc-type lectinen
dc.subjectnitric-oxide synthaseen
dc.subjectbeta-glucan receptoren
dc.subjectfumigatus conidiaen
dc.subjectdendritic cellsen
dc.subjectin-vitroen
dc.subjecthematopoietic transplantationen
dc.subjecthematologic malignanciesen
dc.subjectcorticosteroid treatmenten
dc.subjectcytokine productionen
dc.titleModulation of Immune Signaling and Metabolism Highlights Host and Fungal Transcriptional Responses in Mouse Models of Invasive Pulmonary Aspergillosisen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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