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Generation of Human Monocyte-derived Dendritic Cells from Whole Blood
Published on: December 24, 2016
Monocyte-derived dendritic cells from patients with severe forms of chromoblastomycosis induce CD4+ T cell activation
M Glória Sousa1, E Eid Bou Ghosn, R Ciciro Nascimento
1Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de Sao Paulo, SP, Brazil.
Insights
Dendritic cells (DCs) from chromoblastomycosis patients show altered immune responses. However, incubating these DCs with Fonsecaea pedrosoi conidia reverses anergy and promotes a T helper type 1 response.
Area of Science:
- Immunology
- Mycology
- Dermatology
Background:
- Dendritic cells (DCs) initiate and modulate immune responses.
- Chromoblastomycosis, caused by Fonsecaea pedrosoi, involves impaired T cell responses and low interferon-gamma production in severe cases.
- DCs are the initial defense against F. pedrosoi inoculation.
Purpose of the Study:
- To investigate the interaction between F. pedrosoi and DCs from chromoblastomycosis patients.
- To understand the role of DCs in the immune response to F. pedrosoi.
Main Methods:
- Obtaining DCs from patients with chromoblastomycosis and healthy controls.
- Analyzing the expression of human leucocyte antigen D-related (HLA-DR) and co-stimulatory molecules (CD86) on DCs.
- Incubating DCs with F. pedrosoi conidia.
Main Results:
- DCs from patients showed increased expression of HLA-DR and co-stimulatory molecules.
- Both patient and control DCs upregulated HLA-DR and CD86 expression upon exposure to F. pedrosoi conidia.
- Incubation with F. pedrosoi conidia reversed antigen-specific anergy and induced a T helper type 1 response.
Conclusions:
- DCs from chromoblastomycosis patients exhibit distinct immune profiles.
- F. pedrosoi conidia can modulate DC function to promote an effective T helper type 1 immune response.
- This interaction offers a potential therapeutic avenue for chromoblastomycosis.
Abstract:
Dendritic cells (DCs) have been described as initiators and modulators of the immune response. Recently we have shown a predominant production of interleukin-10 cytokine, low levels of interferon-gamma and inefficient T cell proliferation in patients with severe forms of chromoblastomycosis. Chromoblastomycosis starts with subcutaneous inoculation of Fonsecaea pedrosoi into tissue where DCs are the first line of defence against this microorganism. In the present study, the interaction of F. pedrosoi and DCs obtained from patients with chromoblastomycosis was investigated. Our results showed that DCs from patients exhibited an increased expression of human leucocyte antigen D-related (HLA-DR) and co-stimulatory molecules. In the presence of conidia, the expression of HLA-DR and CD86 was up-regulated by DCs from patients and controls. Finally, we demonstrate the reversal of antigen-specific anergy and a T helper type 1 response mediated by DCs incubated with F. pedrosoi conidea.
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