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.
Original language | English (US) |
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Article number | 108389 |
Journal | Cell Reports |
Volume | 33 |
Issue number | 7 |
DOIs | |
State | Published - Nov 17 2020 |
Keywords
- Aspergillus
- cross-species interaction
- cytomegalovirus
- dendritic cells
- host response
- pulmonary infections
- synergy
- transcriptional networks
- triple RNA-seq
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology