Triple RNA-Seq Reveals Synergy in a Human Virus-Fungus Co-infection Model
- Cell Rep. 2020 Nov 17;33(7):108389. doi: 10.1016/j.celrep.2020.108389.
- 1. Systems Biology and Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), 07745 Jena, Germany.
- 2. University Hospital Würzburg, Medical Hospital II, WÜ4i, 97080 Würzburg, Germany.
- 3. University Hospital Würzburg, Medical Hospital II, WÜ4i, 97080 Würzburg, Germany; The University of Texas MD Anderson Cancer Center, Department of Infectious Diseases, Infection Control and Employee Health, Houston, TX 77030, USA.
- 4. Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Bacterial Infections and Zoonoses, 07743 Jena, Germany.
- 5. Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Hannover-Braunschweig Site, 38124 Braunschweig, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School (MHH) Braunschweig, 38124 Braunschweig, Germany.
- 6. Institute for Experimental Infection Research, TWINCORE-Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Cluster of Excellence RESIST (EXC 2155), Hannover Medical School (MHH), 30625 Hannover, Germany.
- 7. Institute of Molecular Infection Biology (IMIB), University of Würzburg, 97080 Würzburg, Germany; Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), 97080 Würzburg, Germany.
- 8. Systems Biology and Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), 07745 Jena, Germany; Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong S.A.R., China.
- 9. University Hospital Würzburg, Medical Hospital II, WÜ4i, 97080 Würzburg, Germany. Electronic address: [email protected].
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.