Comparative host transcriptome in response to pathogenic fungi identifies common and species-specific transcriptional antifungal host response pathways

Candidiasis, aspergillosis, and mucormycosis cause the majority of nosocomial fungal infections in immunocompromised patients. Using an unbiased transcriptional profiling in PBMCs exposed to the fungal species causing these infections, we found a core host response in healthy individuals that governs effective fungal clearance: it consists of 156 transcripts, involving canonical and non-canonical immune pathways. Systematic investigation of key steps in antifungal host defense revealed fungal-specific signatures. As previously demonstrated, C. albicans induced interferon-related pathways. In contrast, PRRs, ROS production and host glycolytic pathways were down-regulated in response to R. oryzae, and their modulation is associated with ER-stress response. TLR5 was surprisingly identified to be uniquely regulated by A. fumigatus and to control its-induced cytokine release. In conclusion, our data reveals the transcriptional profiles induced by C. albicans, A. fumigatus, and R. oryzae, and describes both the common and specific antifungal host responses that could be exploited for novel therapeutic strategies. Overall design: RNA sequencing profiles of human PBMCs stimulated for 4h and 24h with A. fumigatus, C. albicans and R. oryzae