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.
Authors: Bastian Seelbinder, J. Wallstabe, Lothar Marischen, Esther Weiß, S. Wurster, L. Page, C. Loffler, L. Bussemer, A. L. Schmitt, Thomas Wolf, Jörg Linde, L. Cicin-Sain, J. Becker, U. Kalinke, J. Vogel, Gianni Panagiotou, Hermann Einsele, A. J. Westermann, Sascha Schäuble, Jürgen Löffler
Date Published: 17th Nov 2020
Journal: Cell Rep