Scientific reports · 2021
The network interplay of interferon and Toll-like receptor signaling pathways in the anti-Candida immune response.
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Salgado Ranieri Coelho, Fonseca Dennyson Leandro M, Marques Alexandre H C, da Silva Napoleao Sarah Maria, França Tábata Takahashi, Akashi Karen Tiemi, de Souza Prado Caroline Aliane, Baiocchi Gabriela Crispim, Plaça Desirée Rodrigues, Jansen-Marques Gabriel, Filgueiras Igor Salerno, De Vito Roberta, Freire Paula Paccielli, de Miranda Gustavo Cabral, Camara Niels Olsen Saraiva, Calich Vera Lúcia Garcia, Ochs Hans D, Schimke Lena F, Jurisica Igor, Condino-Neto Antonio, Cabral-Marques Otavio
Аннотация
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.