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


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-kappaB (nuclear factor kappaB) 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.


PubMed ID: 33207195

Projects: A2, B5, INF

Publication type: Not specified

Journal: Cell Rep

Citation: Cell Rep. 2020 Nov 17;33(7):108389. doi: 10.1016/j.celrep.2020.108389.

Date Published: 17th Nov 2020

Registered Mode: Not specified

Authors: B. Seelbinder, J. Wallstabe, L. Marischen, E. Weiss, S. Wurster, L. Page, C. Loffler, L. Bussemer, A. L. Schmitt, T. Wolf, J. Linde, L. Cicin-Sain, J. Becker, U. Kalinke, J. Vogel, G. Panagiotou, H. Einsele, A. J. Westermann, S. Schauble, J. Loeffler

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Created: 10th Feb 2021 at 12:26

Last updated: 17th Jan 2024 at 10:24

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