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Susceptibility and resistance of inbred mice to Paracoccidioides brasiliensis
Abstract:
Nine different inbred strains of mice inoculated intraperitoneally with yeast cells of Paracoccidioides brasiliensis showed significantly varying patterns of susceptibility. The A/SN strain was found to be the most resistant, while BIOD2/nSn, BIO.A and BIOD2/oSn the most susceptible strains. These susceptibility differences were not dependent on the size of challenge inocula and sex of animals. All strains studied showed a mean survival time proportional to the size of inocula used. Although almost all infected male mice presented a shorter survival time when compared with females, significant mortality differences between sexes were found only in two of the strains studied, namely BALB/c and BIOD2/nSn. The H-2 region did not influence the susceptibility pattern since the A/SN and BIO.A strains share the same H-2 haplotype and were respectively highly resistant and susceptible to P. brasiliensis. Furthermore, the presence of C5 and unresponsiveness to lipopolysaccharide had no influence on the mortality data observed. Specific antibodies were detected only in a small number of animals and titres were consistently low, appearing later in the resistant (A/SN) than in a susceptible strain (BIO.A). Omentum, spleen and liver were the most affected organs in both strains, but the susceptible mice had more granulomatous lesions and earlier dissemination of the fungus.
Insights
Mouse strain genetics significantly impact susceptibility to Paracoccidioides brasiliensis infection. Researchers identified specific resistant and susceptible mouse strains, crucial for understanding fungal disease progression.
Area of Science:
- Immunology
- Infectious Diseases
- Genetics
Background:
- Paracoccidioides brasiliensis causes paracoccidioidomycosis, a significant human fungal infection.
- Understanding host genetic factors influencing disease susceptibility is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the influence of different inbred mouse strains on susceptibility to Paracoccidioides brasiliensis.
- To determine if host genetics, sex, or specific immune markers affect disease outcome.
Main Methods:
- Inoculation of nine inbred mouse strains with Paracoccidioides brasiliensis yeast cells.
- Assessment of mortality, survival time, and organ involvement.
- Analysis of H-2 haplotype, C5 complement component, and lipopolysaccharide responsiveness.
Main Results:
- Significant variations in susceptibility were observed among mouse strains; A/SN was most resistant, while BIOD2/nSn, BIO.A, and BIOD2/oSn were most susceptible.
- Susceptibility was independent of inoculum size and sex, though males generally had shorter survival times.
- The H-2 region, C5 presence, and lipopolysaccharide responsiveness did not correlate with mortality patterns.
- Antibody responses were low and delayed in resistant strains compared to susceptible ones.
- Omentum, spleen, and liver were primary affected organs, with greater lesions and fungal dissemination in susceptible mice.
Conclusions:
- Inbred mouse strain genetics are a primary determinant of susceptibility to Paracoccidioides brasiliensis infection.
- Specific genetic factors, not H-2 haplotype or complement/LPS response, dictate differential host response.
- Further research into the genetic basis of resistance and susceptibility can inform therapeutic strategies for paracoccidioidomycosis.

