Interaction between Paracoccidioides brasiliensis and pulmonary dendritic cells induces interleukin-10 production and toll-like receptor-2 expression: possible mechanisms of susceptibility.

Dendritic cells (DCs) are the most effective antigen-presenting cells for inducing cell-mediated immune responses; it is thus important to investigate the role played by lung DCs in the pathogenesis of paracoccidioidomycosis (PCM) and their potential to initiate an immune response in mice susceptible (B10.A) and resistant (A/J) to PCM. Initially, we observed that lung DCs from susceptible mice were more phagocytic than cells from resistant mice, and we observed that phagocytosis in the presence of laminarin was inhibited only in DCs from susceptible mice. DCs from resistant mice produced a low concentration of interleukin (IL)-10, IL-12, and tumor necrosis factor (TNF)- alpha . In contrast, DCs from susceptible mice produced high concentrations of TNF- alpha and IL-10, but IL-10 production was significantly inhibited in the presence of laminarin. We also observed that DCs from Toll-like receptor (TLR)-2 knockout mice displayed defective production of IL-10. After 15 days of Paracoccidioides brasiliensis infection, DCs from susceptible mice produced IL-10 and expressed costimulatory molecules at a low level. We found that expression of the gene for TLR-2 is increased after infection in susceptible, but not resistant, mice. In conclusion, our data suggest that P. brasiliensis induces regulatory DCs in susceptible mice, which promotes IL-10 production and contributes to the susceptibility of mice to P. brasiliensis infection.