Monocyte-Derived Dendritic Cells Can Revert In Vitro Antigen-Specific Cellular Anergy in Active Human Paracoccidioidomycosis
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Citações na Scopus
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Tipo de produção
article
Data de publicação
2021
Título da Revista
ISSN da Revista
Título do Volume
Editora
MDPI
Autores
PASSOS, Erika Cano
MIRANDA, Tatiana Giselle Rodrigues
SADAHIRO, Aya
ALMEIDA, Sandro Rogerio de
Citação
JOURNAL OF FUNGI, v.7, n.3, article ID 201, 16p, 2021
Resumo
We investigated the in vitro effects of two Paracoccidioides brasiliensis antigens on monocyte-derived dendritic cells (moDCs) from patients with paracoccidioidomycosis (PCM). MoDCs from patients with active or treated PCM and non-PCM subjects were generated, stimulated with TNF-alpha, and P. brasiliensis antigens, 43 kDa glycoprotein (gp43) and cell-free antigen (CFA), and analyzed by flow cytometry and enzyme-linked immunosorbent assays (ELISA). Our data revealed that patients with PCM had a high frequency of HLA-DR+ cells, but the treated group had more CD86(+) cells with increased IL-12p40. Patients with active PCM had more CD80(+) moDCs, and as a novel finding, large amounts of chemokine (C-C motif) ligand 18 (CCL18) in the supernatants from their in vitro moDC cultures. Both gp43- and CFA-stimulated moDCs from the patients with PCM successfully reverted the in vitro antigen-specific anergy, inducing a proliferative response. However, CFA-stimulated moDCs led to higher lymphoproliferation, with increased IFN-gamma and TNF-alpha in the cells from the patients with active PCM compared with gp43. These original results combined with constant IL-10 and increased IL-12p40 levels suggest that a more complex antigen, such as CFA, may be a better inducer of the protective Th1 immune response than purified gp43 is, and a suitable target for future studies on anti-P. brasiliensis dendritic cell (DC)-based vaccines.
Palavras-chave
Paracoccidioides brasiliensis, paracoccidioidomycosis, dendritic cells, cytokines, coculture, gp43, cell-free antigen
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