The low efficiency of dendritic cells and macrophages from mice susceptible to Paracoccidioides brasiliensis in inducing a Th1 response

Abstract

In the present study we evaluated T cell proliferation and Th lymphokine patterns in response to gp43 from Paracoccidioides brasiliensis presented by isolated dendritic cells from susceptible and resistant mice. T cell proliferation assays showed that dendritic cells from susceptible mice were less efficient than those from resistant mice. The pattern of T cell lymphokines stimulated by dendritic cells was always Th1, although the levels of IL-2 and IFN-g were lower in T cell cultures from susceptible mice. To determie whether different antigen-presenting cells such as macrophages and dendritic cells stimulated different concentrations of Th1 lymphokines, the production of IFN-g and IL-2 was measured. It was observed that dendritic cells were more efficient than macrophages in stimulating lymphoproliferation in resistant mice. However, no significant difference was observed for IFN-g or IL-2 production. When cells from susceptible mice were used, macrophages were more efficient in stimulating lymphoproliferation than dendritic cells, but no difference was observed in the production of Th1 cytokine. Taken together, these results suggest the lower efficiency of dendritic cells and macrophages from B10.A mice in stimulating T cells that secrete Th1 lymphokines in vitro, an effect that may be involved in the progression of the disease in vivo.

Dual Role for Nitric Oxide in Paracoccidioidomycosis: Essential for Resistance, but Overproduction Associated with Susceptibility

“…‫,ء‬ significant difference (p Ͻ 0.05) between AG-treated vs untreated group. MHC class II expression (8) and that macrophages from susceptible mice are less effective in Ag presentation (25). However, our results with IA k expression are in contrast to those reports, as we showed that macrophage IA k expression of susceptible mice was not impaired and actually was higher in susceptible than in resistant mice throughout the infection.…”

Murine Dendritic Cells Transcriptional Modulation upon Paracoccidioides brasiliensis Infection

“…Here, we demonstrate the increased production of IL-12 mRNA and protein by BALB/c DCs infected with P. brasiliensis for 6 hours. Considering that this mouse lineage has intermediate resistance to P. brasiliensis infection [13], we could draw a parallel with previous observations demonstrating that DCs derived from resistant mice (A/J) stimulate a Th1 response in vitro more efficiently than DCs derived from susceptible mice (B10.A) when pulsed with the immunodominant P. brasiliensis antigen, gp43 [25]. Diverse antigen-recognition and -processing mechanisms in DCs from resistant and susceptible mice, which would give rise to differential production of IL-12, could be involved in determining susceptibility to this fungus.…”

Prophylactic and Therapeutic Vaccination Using Dendritic Cells Primed with Peptide 10 Derived from the 43-Kilodalton Glycoprotein of Paracoccidioides brasiliensis

“…T-cell activation and proliferation can lead to immunity or to tolerance, thus generating effector or regulatory T cells and different patterns of cytokines (36,37). The regulation of T-cell response by DCs in systemic and subcutaneous mycosis has been studied in Histoplasma capsulatum (15), Coccidioides posadasii (13), Sporothrix schenckii (44), and P. brasiliensis (1). The role of DCs in vaccination is a promising area for study.…”