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

Abstract Incidences 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 mec...

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Autores principales:	Shiv D. Kale, Tariq Ayubi, Dawoon Chung, Nuria Tubau-Juni, Andrew Leber, Ha X. Dang, Saikumar Karyala, Raquel Hontecillas, Christopher B. Lawrence, Robert A. Cramer, Josep Bassaganya-Riera
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3e1eb754a5404bed9918e73fc0cf64c9
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spelling	oai:doaj.org-article:3e1eb754a5404bed9918e73fc0cf64c92021-12-02T15:05:18ZModulation of Immune Signaling and Metabolism Highlights Host and Fungal Transcriptional Responses in Mouse Models of Invasive Pulmonary Aspergillosis10.1038/s41598-017-17000-12045-2322https://doaj.org/article/3e1eb754a5404bed9918e73fc0cf64c92017-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-17000-1https://doaj.org/toc/2045-2322Abstract Incidences 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.Shiv D. KaleTariq AyubiDawoon ChungNuria Tubau-JuniAndrew LeberHa X. DangSaikumar KaryalaRaquel HontecillasChristopher B. LawrenceRobert A. CramerJosep Bassaganya-RieraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-25 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shiv D. Kale Tariq Ayubi Dawoon Chung Nuria Tubau-Juni Andrew Leber Ha X. Dang Saikumar Karyala Raquel Hontecillas Christopher B. Lawrence Robert A. Cramer Josep Bassaganya-Riera Modulation of Immune Signaling and Metabolism Highlights Host and Fungal Transcriptional Responses in Mouse Models of Invasive Pulmonary Aspergillosis
description	Abstract Incidences 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.
format	article
author	Shiv D. Kale Tariq Ayubi Dawoon Chung Nuria Tubau-Juni Andrew Leber Ha X. Dang Saikumar Karyala Raquel Hontecillas Christopher B. Lawrence Robert A. Cramer Josep Bassaganya-Riera
author_facet	Shiv D. Kale Tariq Ayubi Dawoon Chung Nuria Tubau-Juni Andrew Leber Ha X. Dang Saikumar Karyala Raquel Hontecillas Christopher B. Lawrence Robert A. Cramer Josep Bassaganya-Riera
author_sort	Shiv D. Kale
title	Modulation of Immune Signaling and Metabolism Highlights Host and Fungal Transcriptional Responses in Mouse Models of Invasive Pulmonary Aspergillosis
title_short	Modulation of Immune Signaling and Metabolism Highlights Host and Fungal Transcriptional Responses in Mouse Models of Invasive Pulmonary Aspergillosis
title_full	Modulation of Immune Signaling and Metabolism Highlights Host and Fungal Transcriptional Responses in Mouse Models of Invasive Pulmonary Aspergillosis
title_fullStr	Modulation of Immune Signaling and Metabolism Highlights Host and Fungal Transcriptional Responses in Mouse Models of Invasive Pulmonary Aspergillosis
title_full_unstemmed	Modulation of Immune Signaling and Metabolism Highlights Host and Fungal Transcriptional Responses in Mouse Models of Invasive Pulmonary Aspergillosis
title_sort	modulation of immune signaling and metabolism highlights host and fungal transcriptional responses in mouse models of invasive pulmonary aspergillosis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3e1eb754a5404bed9918e73fc0cf64c9
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_version_	1718388885990408192

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

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