PATHOGENICITY AND IMMUNOGENICITY OF PARACOCCIDIOIDES-BRASILIENSIS ISOLATES IN THE HUMAN-DISEASE AND IN AN EXPERIMENTAL MURINE MODEL

The pathogenicity and immunogenicity of six recently isolated Paracocc idioides brasiliensis samples derived from patients presenting distinc t and well defined clinical forms of paracoccidioidomycosis (PCM) were compared as to their virulence, tropism to different organs and abili ty to induce specific cellular and humoral immune response in suscepti ble (B10.A) inbred mice. Isolates Pb44 and Pb47 were obtained from acu te cases, Pb50 from a chronic severe form, Pb45 from a chronic moderat e case and both Pb56 and Pb57 from chronic mild forms of PCM. Pathogen icity and tropism of each fungal sample were evaluated by LD50% estima tion, examination of gross lesions on various organs at 2, 4, 12 and 1 6 weeks post-infection, and by colony-forming unit (CFU) counts in the lungs at week 16 post-infection of mice. Fungal tropism in human PCM and in B10.A mice was always dissociated. A well defined relationship between virulence of the fungal sample and the clinical findings of th e correspondent patient was not evident, although a tendency to higher LD50% and less intense paracoccidioidic lesions was observed in mice infected with Pb56 and Pb57. The specific DTH response patterns varied according to the infectant sample, but positive DTH reactions at the beginning of the infection and a tendency to anergy or low DTH respons es at week 12 and/or week 16 post-infection were always observed. A co rrespondence between the DTH response in humans and in mice was notice able only when the isolates from the most benign cases (Pb56 and Pb57) were considered. The specific antibody patterns in mice and in the co rrespondent patients were also not analogous. Collectively, these resu lts indicate that an association between the fungal pathogenicity and immunogenicity in the human disease and in susceptible mice was discer nible only when isolates obtained from very mild cases (Pb56 and Pb57) were considered.