Genome-Wide Association Study Reveals CLEC7A and PROM1 as Potential Regulators of Paracoccidioides brasiliensis-Induction of Cytokine Production in Peripheral Blood Mononuclear Cells-Reference-Cited by-同舟云学术

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

Published:2023-03-30 Issue:4 Volume:9 Page:428
ISSN:2309-608X
Container-title:Journal of Fungi
language:en
Short-container-title:JoF

Author:

de Figueiredo Ana Marina B.¹,dos Santos Jéssica Cristina²^ORCID,Kischkel Brenda²³^ORCID,Ardiansyah Edwin²,Oosting Marije²,Guimarães Matos Grazzielle¹,Barreto Neves Oliveira Iara¹,van de Veerdonk Frank²,Netea Mihai G.²,Soares Célia Maria de Almeida⁴^ORCID,Ribeiro-Dias Fátima¹^ORCID,Joosten Leo A. B.²^ORCID

Affiliation:

1. Laboratório de Imunidade Natural (LIN), Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia 74605-050, Goiás, Brazil

2. Department of Internal Medicine, Radboud Institute for Molecular Sciences (RILMS) and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, 6524 Nijmegen, The Netherlands

3. Departamento de Microbiologia, Instituto de Ciência Biomédicas, Universidade de São Paulo, São Paulo 05508-000, São Paulo, Brazil

4. Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia 74690-900, Goiás, Brazil

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.

Funder

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–Brasil

PRONEM

National Institute of Science and Technology of the strategies in host-pathogen interaction

Fundação de Amparo à Pesquisa do Estado de Goiás (FAPEG), Brazil

National Council for Scientific and Technological Development (CNPq), Brazil

Publisher

MDPI AG

Subject

Plant Science,Ecology, Evolution, Behavior and Systematics,Microbiology (medical)

Link

https://www.mdpi.com/2309-608X/9/4/428/pdf

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