The development of the appropriate CD4 Th subset is important for disease resolution and several studies have shown that different outcomes of a disease can be obtained by influencing the commitment of precursors to either, Th1 or Th2 lineage. Dendritic cells (DCs) are able to initiate response in naïve T cells and they also participate in Th cell education. In the present study we demonstrated that purified gp43 lead to down-regulation of MHC-II and adhesion properties of immature DCs and in LPS-induced DCs maturation. It was also shown that purified gp43 from Paracoccidioides brasiliensis has the same inhibitory effect on IL-12 release. Mice infected with Paracoccidioides brasiliensis that received DCs plus gp43 plus LPS had a significant increase of the lung colony forming units when compared with control (not immunized) or those that received only DCs plus LPS. Thus, the granuloma morphology seen in immunized mice was different when compared with non-immunized controls. These data suggest that gp43 affects many functions of the host cells, indicating that these alterations might be used by Paracoccidioides brasiliensis to reduce the effectiveness of the immune response thus facilitating the establishment and fate of primary infection in susceptible host.