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.
RESUMO A ovinocultura encontra-se em constante crescimento mundialmente. Nessa atividade, a mastite é uma das enfermidades que acometem as ovelhas, gerando desmame de cordeiros leves, ou até mesmo a perda definitiva da função da glândula mamária. Sendo assim, seu diagnóstico deve ser precoce, evitando-se essas perdas na produção. Nesse estudo, foram avaliadas 413 ovelhas, destas 300 se apresentavam lactantes e foram inseridas nas avaliações. Para isso, foram coletados 2mL de amostra de leite de cada glândula mamária e adicionados 2mL de reagente do California Mastitis Test (CMT). Após homogeneização, a reação foi interpretada, considerando-se 5 graus de aglutinação: (-) sem alteração de consistência, (+) presença de gel ou formas espessas de lodo, mas sem mobilidade, (++) forma espessa de gel grumoso, com movimentação em direção ao centro, (+++) formas de gel distintas com adesão à parte inferior da raquete para CMT e (MC: mastite clínica) consistência grumosa, mesmo sem adição do reagente. O objetivo desse estudo foi realizar um levantamento da prevalência de mastite subclínica em ovelhas na região metropolitana de Umuarama-PR. Das propriedades avaliadas, 90% continha animais positivos. Dentre os animais avaliados, 55,6% apresentaramse positivos no teste, com uma variação de 0 a 90,4% entre as propriedades. Quanto à mastite clínica, houve incidência de 2 a 34% de acometimento dos animais entre as propriedades. Sendo assim, conclui-se que a mastite clínica e subclínica são enfermidades de grande acometimento dos animais presentes nas propriedades de criação dessa espécie.
Here we employed a stepwise, integrative, and systems immunology approach to unravel the human immune responses to C. albicans and C. auris by analyzing publicly available human transcriptome data. Modular gene co-expression analysis revealed an interplay between Toll-like Receptors (TLR) and Interferon (IFN) networks. Enrichment analyses and hierarchical clustering revealed that this relationship is consistently triggered in peripheral white blood cells, peripheral blood mononuclear cells, and dendritic cell transcriptomes, involving IFN-γ, IFN-α/β- (e.g., ISGs, IRFs, SOCS, and GBPs) and TLR-associated molecules (TLR3,4,7/8,9, and TRAF-mediated NF-κB). These TLR- and IFN-associated genes cluster and increase their correlation levels after Candida stimulation, forming a highly interconnected interferome network, which contains an immune overlap with the anti-viral responses. Notably, our analysis shed new lights on the molecular basis of several genes associated with inborn errors of immunity that cause host susceptibility to fungal infections such as Candida spp., which reinforce our transcriptomic findings.
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. (C. albicans and C. auris) by performing a meta-analysis of microarray, bulk, and single-cell RNA-sequencing (RNASeq) of blood transcriptome data. We identified that C. albicans activates a network interplay of signaling molecules commonly involved in both toll-like receptor (TLR) and interferon (IFN) signaling cascades. These molecules form a highly interconnected interferome network, which contains an immune overlap with the anti-viral responses. scRNAseq data confirmed that genes commonly identified by the three transcriptomic methods present a consistent upregulation pattern across innate immune and adaptive cells (CD4+, CD8+, and CD19+ lymphocytes). Thus, our results shed new lights on the molecular basis of immune response to Candida spp.
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