Influence of the genetic pattern and sex of mice in experimental paracoccidioidomycosis.

Eight genetically different strains of mice were compared regarding the dissemination of Paracoccidioides brasiliensis to the lungs, liver and omentum/pancreas, DTH responses and specific antibody production at 16 weeks after intraperitoneal infection with Pb18, a virulent P. brasiliensis isolate. The degree of dissemination of the infection varied: B10.A and C57B1/6, the most susceptible mouse strains, had positive cultures and high colony-forming unit (CFU) counts in all analysed organs. DBA/2 and A/Sn mice had negative cultures, being thus classified as the most resistant strains. CBA/J, C3H/HeJ, F1(A/SnxB10.A) and BALB/c mice were regarded as relatively resistant, since discrete fungal growth was observed only in one or two of the studied organs. All mouse strains, except B10.A mice, produced specific DTH responses which did not seem to be associated with the severity of disease. Production of high levels of specific antibodies was found in all strains except in the DBA/2 and C57B1/6 mice. The influence of the host sex on the outcome of paracoccidioidomycosis was evident only in susceptible animals: female B10.A mice displayed lower CFU counts in the three examined organs, whereas no differences were found between male and female A/Sn animals. The higher resistance of female B10.A mice was not accompanied by differences in their capacity to maintain a DTH reaction, nor in their production of antibody. This fact argues against the widely believed association of susceptibility to P. brasiliensis infection with both impaired DTH reactivity and increased humoral response.

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 Paracoccidioides brasiliensis samples derived from patients presenting distinct and well defined clinical forms of paracoccidioidomycosis (PCM) were compared as to their virulence, tropism to different organs and ability to induce specific cellular and humoral immune response in susceptible (B10.A) inbred mice. Isolates Pb44 and Pb47 were obtained from acute cases, Pb50 from a chronic severe form, Pb45 from a chronic moderate case and both Pb56 and Pb57 from chronic mild forms of PCM. Pathogenicity and tropism of each fungal sample were evaluated by LD50% estimation, examination of gross lesions on various organs at 2, 4, 12 and 16 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 the 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 responses at week 12 and/or week 16 post-infection were always observed. A correspondence between the DTH response in humans and in mice was noticeable only when the isolates from the most benign cases (Pb56 and Pb57) were considered. The specific antibody patterns in mice and in the correspondent patients were also not analogous. Collectively, these results indicate that an association between the fungal pathogenicity and immunogenicity in the human disease and in susceptible mice was discernible only when isolates obtained from very mild cases (Pb56 and Pb57) were considered.