Seelbinder, BastianWallstabe, JuliaMarischen, LotharWeiss, EstherWurster, SebastianPage, LukasLöffler, ClaudiaBussemer, LydiaSchmitt, Anna-LenaWolf, ThomasLinde, JörgCicin-Sain, LukaBecker, JenniferKalinke, UlrichVogel, JörgPanagiotou, GianniEinsele, HermannWestermann, Alexander JSchäuble, SaschaLoeffler, Juergen2020-12-082020-12-082020-11-17Cell Rep. 2020 Nov 17;33(7):108389. doi: 10.1016/j.celrep.2020.108389.3320719510.1016/j.celrep.2020.108389http://hdl.handle.net/10033/622636High-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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Aspergilluscross-species interactioncytomegalovirusdendritic cellshost responsepulmonary infectionssynergytranscriptional networkstriple RNA-seqArticle2211-1247Cell reports