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

Abstract

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.

Paracoccidioides brasiliensis Interferes on Dendritic Cells Maturation by Inhibiting PGE2 Production

“…Our findings support studies with PCM patients showing that only DCs from treated patients are effectively activated and show high expression of HLA-DR, CD86 and DC-SIGN, as well as IL-12 production. Thus, during active disease a dysregulation in DCs maturation can be detected and consequent fail to provide optimal costimulation for T cell proliferation may occur [ 81 ].…”

Altered distribution of peripheral blood dendritic cell subsets in patients with pulmonary paracoccidioidomycosis

“…Several reports have shown the importance of these cells in experimental PCM models (Almeida and Lopes, 2001;Ferreira and Almeida, 2006;Ferreira et al, 2011Ferreira et al, , 2007Magalhães et al, 2012;Pina et al, 2013;Silvana dos Santos et al, 2011;Tavares et al, 2012), but few studies have been performed in patients. Some researchers have demonstrated an altered distribution of DCs in the skin and/or mucocutaneous lesions from PCM-p (Gimenez et al, 1987;Kaminagakura et al, 2007;Pagliari and Sotto, 2003), and others have found that monocytederived DCs of treated PCM-p show a higher expression of HLA-DR, DC-SIGN, CD86 and higher production of IL-12p40 than patients with active disease and healthy individuals (Sato et al, 2011). Recently, Fernandes et al (2015) showed that P. brasiliensis yeast cells impair the maturation of monocyte-derived DCs of normal individuals.…”

Protection against Paracoccidioides brasiliensis infection in mice treated with modulated dendritic cells relies on inhibition of interleukin‐10 production by CD8+ T cells

“…These observations indicate that DC modulation is an important keystone event that must be directed towards the development of immune responses in deficient individuals. That is the case of Paracoccidioides brasiliensis ‐infected patients …”