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

Abstract

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.

Keywords

• Paracoccidioidomycosis
• GWAS
• genetic polymorphism
• <i>CLEC7A</i>
• <i>PROM1</i>
• CD38