Pattern of immune response to GP43 from Paracoccidioides brasiliensis in susceptible and resistant mice is influenced by antigen-presenting cells.

Paracoccidioidomycosis (PCM), endemic in Latin America, is a progressive systemic mycosis caused by Paracoccidioides brasiliensis. The infection can evolve to different clinical forms that are associated with various degrees of suppressed cell-mediated immunity. In the murine model, A/Sn and B10.A isogenic strains of mice are known to be resistant and susceptible, respectively, to this fungal infection. Assuming that the effector immune response is a consequence of the preferential activation of either Th1 or Th2 subsets, in the present work we evaluated the importance of two antigen-presenting cells (APCs), macrophages and B cells, in the development of the immune response to P. brasiliensis. In resistant mice, purified gp43, the main antigenic component of P. brasiliensis, seems to have been preferentially presented by macrophages and stimulated Th1 lymphokine production. On the other hand, in susceptible animals gp43 was distinguishably presented by B cells, which led to stronger activation of Th2 subsets. Moreover, T cells from resistant mice responded as those from susceptible animals when stimulated by gp43 presented by APCs from susceptible mice and vice versa, indicating that there are no significant differences in the T cell repertoires from A/Sn and B10.A mice. When T cells from F1 (A/Sn x B10.A) mice were stimulated by gp43 presented by APCs from A/Sn or B10.A, impaired behavior of B10.A macrophages in activating Th1 cells and a B10.A B cell tendency to stimulate T cells that secrete higher levels of IL-10 were observed. Taken together, our results suggest that APCs may be implicated in the outcome of P. brasiliensis infection.