Genome-Wide Association Study Reveals CLEC7A and PROM1 as Potential Regulators of Paracoccidioides brasiliensis-Induction of Cytokine Production in Peripheral Blood Mononuclear Cells

Autor: Ana Marina B. de Figueiredo, Jéssica Cristina dos Santos, Brenda Kischkel, Edwin Ardiansyah, Marije Oosting, Grazzielle Guimarães Matos, Iara Barreto Neves Oliveira, Frank van de Veerdonk, Mihai G. Netea, Célia Maria de Almeida Soares, Fátima Ribeiro-Dias, Leo A. B. Joosten
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Fungi, Vol 9, Iss 4, p 428 (2023)
Druh dokumentu: article
ISSN: 2309-608X
DOI: 10.3390/jof9040428
Popis: Paracoccidioidomycosis (PCM) is a systemic mycosis caused by fungi of the genus Paracoccidioides and the different clinical forms of the disease are associated with the host immune responses. Quantitative trait loci mapping analysis was performed to assess genetic variants associated with mononuclear-cells-derived cytokines induced by P. brasiliensis on 158 individuals. We identified the rs11053595 SNP, which is present in the CLEC7A gene (encodes the Dectin-1 receptor) and the rs62290169 SNP located in the PROM1 gene (encodes CD133) associated with the production of IL-1β and IL-22, respectively. Functionally, the blockade of the dectin-1 receptor abolished the IL-1β production in P. brasiliensis-stimulated PBMCs. Moreover, the rs62290169-GG genotype was associated with higher frequency of CD38+ Th1 cells in PBMCs cultured with P. brasiliensis yeasts. Therefore, our research indicates that the CLEC7A and PROM1 genes are important for the cytokine response induced by P. brasiliensis and may influence the Paracoccidioidomycosis disease outcome.
Databáze: Directory of Open Access Journals
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