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Delayed-type hypersensitivity response in an isogenic murine model of paracoccidioidomycosis
R dos A Fazioli1, L M Singer-Vermes, S S Kashino
1Departamento de Imunologia, Universidade de São Paulo, Brasil.
Abstract:
The specific delayed-type hypersensitivity (DTH) response was evaluated in resistant (A/SN) and susceptible (B10.A) mice intraperitoneally infected with yeasts from a virulent (Pb18) or from a non-virulent (Pb265) Paracoccidioides brasiliensis isolates. Both strains of mice were footpad challenged with homologous antigens. Pb18 infected A/SN mice developed an evident and persistent DTH response late in the course of the disease (90th day on) whereas B10.A animals mounted a discrete and ephemeral DTH response at the 14th day post-infection. A/SN mice infected with Pb265 developed cellular immune responses whereas B10.A mice were almost always anergic. Histological analysis of the footpads of infected mice at 48 hours after challenge showed a mixed infiltrate consisting of predominantly mononuclear cells. Previous infection of resistant and susceptible mice with Pb18 did not alter their DTH responses against heterologous unrelated antigens (sheep red blood cells and dinitrofluorobenzene) indicating that the observed cellular anergy was antigen-specific. When fungal related antigens (candidin and histoplasmin) were tested in resistant mice, absence of cross-reactivity was noted. Thus, specific DTH responses against P. brasiliensis depend on both the host's genetically determined resistance and the virulence of the fungal isolate.
Insights
Host resistance and fungal virulence dictate specific delayed-type hypersensitivity (DTH) responses to Paracoccidioides brasiliensis. This study reveals how mouse genetics and yeast strain impact DTH reactions, crucial for understanding fungal infections.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Delayed-type hypersensitivity (DTH) is a critical immune response in fungal infections.
- Paracoccidioides brasiliensis (P. brasiliensis) causes paracoccidioidomycosis, a significant mycosis in Latin America.
- Understanding host-pathogen interactions is key to managing P. brasiliensis infections.
Purpose of the Study:
- To investigate the specific DTH responses in genetically resistant (A/SN) and susceptible (B10.A) mice infected with virulent (Pb18) and non-virulent (Pb265) P. brasiliensis isolates.
- To determine the influence of host genetic background and fungal isolate virulence on DTH reactions.
- To assess the antigen-specificity of the observed immune responses.
Main Methods:
- Intraperitoneal infection of mice with P. brasiliensis isolates.
- Footpad challenge with homologous antigens to elicit DTH responses.
- Histological analysis of footpad infiltrates.
- Testing DTH responses against unrelated and related fungal antigens to assess specificity.
Main Results:
- Resistant mice infected with virulent P. brasiliensis showed a persistent DTH response, while susceptible mice had a weak, transient response.
- Infection with non-virulent P. brasiliensis led to cellular immune responses in resistant mice but anergy in susceptible mice.
- The observed anergy was antigen-specific, as DTH responses to unrelated antigens remained unaltered.
- No cross-reactivity was observed with other fungal antigens in resistant mice.
Conclusions:
- Specific DTH responses to P. brasiliensis are contingent upon both the host's genetic predisposition to resistance and the virulence of the infecting fungal strain.
- These findings highlight the complex interplay between host immunity and pathogen factors in determining disease outcomes.
- The study underscores the importance of antigen-specific DTH in P. brasiliensis infections.