Monocyte-Derived Dendritic Cells Can Revert In Vitro Antigen-Specific Cellular Anergy in Active Human Paracoccidioidomycosis.
Paula Keiko SatoTelma Miyuki OshiroÉrika Cano PassosTatiana Giselle Rodrigues MirandaConstância Lima DiogoClaudia de Abreu FonsecaAya SadahiroSandro Rogério de AlmeidaMaria Aparecida Shikanai YasudaPublished in: Journal of fungi (Basel, Switzerland) (2021)
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-α, 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-γ and TNF-α 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.
Keyphrases
- dendritic cells
- immune response
- high frequency
- regulatory t cells
- induced apoptosis
- cell free
- flow cytometry
- cell cycle arrest
- rheumatoid arthritis
- transcranial magnetic stimulation
- endothelial cells
- cell death
- endoplasmic reticulum stress
- oxidative stress
- toll like receptor
- newly diagnosed
- high throughput
- inflammatory response
- high resolution
- big data
- current status
- machine learning
- heat shock protein
- circulating tumor cells
- artificial intelligence
- deep learning