The network interplay of interferon and Toll-like receptor signaling pathways in the anti-Candida immune response
Ranieri Coelho Salgado, Dennyson Leandro M. Fonseca, Alexandre H. C. Marques, Sarah Maria da Silva Napoleão, Tábata Takahashi França, Karen Tiemi Akashi, Caroline Aliane de Souza Prado, G. Baiocchi, Desirée Rodrigues Plaça, Gabriel Jansen-Marques, Igor Salerno Filgueiras, Roberta De Vito, Paula Paccielli Freire, Gustavo Cabral de Miranda, Niels Olsen Saraiva Câmara, Vera Lúcia Garcia Calich, Hans D. Ochs, Lena F. Schimke, Igor Jurišica, Antônio Condino‐Neto, Otávio Cabral-Marques
Abstract
Fungal infections represent a major global health problem affecting over a billion people that kills more than 1.5 million annually. In this study, we employed an integrative approach to reveal the landscape of the human immune responses to Candida spp. through meta-analysis of microarray, bulk, and single-cell RNA sequencing (scRNA-seq) data for the blood transcriptome. 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 are several types I IFN, indicating an overlap with antiviral immune responses. scRNA-seq data confirmed that genes commonly identified by the three transcriptomic methods show cell type-specific expression patterns in various innate and adaptive immune cells. These findings shed new light on the anti-Candida immune response, providing putative molecular pathways for therapeutic intervention.