The network interplay of interferon and toll-like receptor signaling pathways in the anti-Candida immune response

Fungal infections represent a major global health problem that affects over a billion people and kills more than 1.5 million individuals annually. Here we employed an integrative approach to unravel the landscape of the human immune responses to Candida spp. by performing a meta-analysis of microarray, bulk, and single-cell RNA-sequencing (RNASeq) of blood transcriptome data. We identified across these different studies a consistent interconnected network interplay of signaling molecules involved in both toll-like receptor (TLR) and interferon (IFN) signaling cascades that is activated in response to different Candida species (C. albicans, C. auris, C. glabrata, C. parapsilosis, and C. tropicalis). Among these molecules, there are several types I IFN, indicating an overlap with the anti-viral immune responses. scRNAseq data confirmed that genes commonly identified by the three transcriptomic methods present a cell-type specific expression patterns across innate and adaptive immune cells. Thus, these data shed new lights on the anti-candida immune response, providing putative molecular pathways for therapeutic intervention.