Triple RNA-Seq Reveals Synergy in a Human Virus-Fungus Co-infection Model

Seelbinder B, Wallstabe J, Marischen L, Weiss E, Wurster S, Page L, Loeffler C, Bussemer L, Schmitt AL, Wolf T, Linde J, Cicin-Sain L, Becker J, Kalinke U, Vogel J, Panagiotou G, Einsele H, Westermann AJ, Schaeuble S, Loeffler J (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 33

Article Number: 108389

Journal Issue: 7

DOI: 10.1016/j.celrep.2020.108389

Abstract

High-throughput RNA sequencing (RNA-seq) is routinely applied to study diverse biological processes; however, when performed separately on interacting organisms, systemic noise intrinsic to RNA extraction, library preparation, and sequencing hampers the identification of cross-species interaction nodes. Here, we develop triple RNA-seq to simultaneously detect transcriptomes of monocyte-derived dendritic cells (moDCs) infected with the frequently co-occurring pulmonary pathogens Aspergillus fumigatus and human cytomegalovirus (CMV). Comparing expression patterns after co-infection with those after single infections, our data reveal synergistic effects and mutual interferences between host responses to the two pathogens. For example, CMV attenuates the fungus-mediated activation of pro-inflammatory cytokines through NF-κB (nuclear factor κB) and NFAT (nuclear factor of activated T cells) cascades, while A. fumigatus impairs viral clearance by counteracting viral nucleic acid-induced activation of type I interferon signaling. Together, the analytical power of triple RNA-seq proposes molecular hubs in the differential moDC response to fungal/viral single infection or co-infection that contribute to our understanding of the etiology and, potentially, clearance of post-transplant infections.

Involved external institutions

Universitätsklinikum Würzburg DE Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie (Hans-Knöll-Institut (HKI)) / Leibniz Institute for Natural Product Research and Infection Biology DE Germany (DE) Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE) Friedrich-Loeffler-Institut (FLI), Bundesforschungsinstitut für Tiergesundheit DE Germany (DE) Julius-Maximilians-Universität Würzburg DE Germany (DE)

How to cite

APA:

Seelbinder, B., Wallstabe, J., Marischen, L., Weiss, E., Wurster, S., Page, L.,... Loeffler, J. (2020). Triple RNA-Seq Reveals Synergy in a Human Virus-Fungus Co-infection Model. Cell Reports, 33(7). https://doi.org/10.1016/j.celrep.2020.108389

MLA:

Seelbinder, Bastian, et al. "Triple RNA-Seq Reveals Synergy in a Human Virus-Fungus Co-infection Model." Cell Reports 33.7 (2020).

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