Characterization of Monocyte‐Derived Dendritic Cells from Patients with Active and Treated Paracoccidioidomycosis

• Published in: Scandinavian journal of immunology Vol. 74; no. 6; pp. 609 - 618
• Main Authors: Sato, P. K., Oshiro, T. M., Diogo, C. L., Passos, É. C., Shikanai‐Yasuda, M. A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2011
• Subjects: B7-2 Antigen - immunology; CD11c Antigen - immunology; CD86 antigen; Cell Differentiation; Cells, Cultured; DC-SIGN protein; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - immunology; Histocompatibility antigen HLA; Humans; Immunity; Interleukin 10; Interleukin 12; Monocytes; Mycosis; Paracoccidioides brasiliensis; Paracoccidioidomycosis - immunology; Paracoccidioidomycosis - therapy; South American blastomycosis; Tumor necrosis factor- alpha
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1111/j.1365-3083.2011.02614.x

Cellular immune responses are a significant defence mechanism in human paracoccidioidomycosis (PCM), an endemic mycosis in Latin America; however, little is known about the role of dendritic cells (DCs) in human PCM. We investigated monocyte‐derived DCs from patients with treated (TP) and active PCM (AP) compared with healthy non‐PCM donors (CO). DCs from the TP group showed higher expression of HLA‐DR, CD86 and DC‐SIGN compared with CO, whereas AP showed similar expression to CO. Production of IL‐10 was downregulated by TNF‐α in all groups and lower levels were observed in untreated DCs from AP compared with CO. Conversely, IL‐12p40 was significantly upregulated in the DCs of the TP group. TNF‐α‐activated DCs from the CO group produced significantly lower levels of IL‐12p40 when differentiated from magnetic‐sorted monocytes (MACS) compared with adhered monocyte‐derived DCs. This comparison in the TP group revealed similar levels of IL‐12p40, suggesting a T cell–independent increase in the production of IL‐12p40. Higher expression of surface molecules with increased IL‐12p40 may indicate a better activation of DCs after the treatment of PCM. Our findings suggest that DCs may be crucial in the protective response to Paracoccidioides brasiliensis and that in vitro‐generated DCs might be useful in enhancing antifungal immunity, especially during active PCM.