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Increased tissue resistance in the nude mouse against Candida albicans without altering strain-dependent differences
A Fulurija1, R B Ashman, J M Papadimitriou
1Department of Pathology, University of Western Australia, Nedlands, Australia.
Abstract:
Strain differences in tissue responses to infection with Candida albicans were examined in nude mice having susceptible (CBA/CaH) and resistant (BALB/c) parentage. Homozygous (nu/nu) mice of both strains were more resistant to systemic infection with C. albicans than heterozygous (nul+) littermates as indicated by a reduction in both the severity of tissue damage and colony counts in the brain and kidney. However, the tissue lesions in nu/nu CBA/CaH mice were markedly more severe than those in nu/nu mice with the BALB/c background. This pattern was reflected in the greater fungal burden in the CBA/CaH strain. Analysis of cDNA from infected tissues using a competitive polymerase chain reaction excluded interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), and interleukin 6 (IL-6) as mediators of the enhanced resistance of the nude mice. The results confirm that the different patterns of lesion severity in BALB/c and CBA/CaH mice do not involve T lymphocyte-mediated pathology, and are consistent with the hypothesis that strain-dependent tissue damage is not dependent on the effector function of macrophages or their precursors.
Insights
Nude mice showed increased resistance to Candida albicans infection. However, strain differences in tissue damage and fungal burden persisted, independent of T-cell responses or key cytokines like interferon-gamma.
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- Strain differences in host response to Candida albicans infection are well-documented.
- Nude mice (nu/nu) lack T lymphocytes, offering a model to study T-cell independent immunity.
- Susceptible (CBA/CaH) and resistant (BALB/c) mouse strains provide a genetic basis for differential responses.
Purpose of the Study:
- To investigate strain-specific tissue responses to Candida albicans infection in nude mice.
- To determine the role of T lymphocytes and specific cytokines in mediating observed resistance and susceptibility differences.
- To explore the contribution of macrophage function to strain-dependent tissue damage.
Main Methods:
- Comparative analysis of tissue damage severity and fungal colony counts in homozygous (nu/nu) and heterozygous (nu/+) nude mice of CBA/CaH and BALB/c strains following systemic C. albicans infection.
- Competitive polymerase chain reaction (PCR) analysis of infected tissues to quantify messenger RNA (mRNA) levels of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6).
Main Results:
- Homozygous nude mice (nu/nu) exhibited greater resistance to systemic C. albicans infection than heterozygous littermates (nu/+), evidenced by reduced tissue damage and fungal load in the brain and kidney.
- Despite enhanced resistance in nude mice, CBA/CaH background mice displayed significantly more severe tissue lesions and a higher fungal burden compared to BALB/c background nude mice.
- Analysis of cDNA excluded IFN-γ, TNF-α, and IL-6 as mediators of the enhanced resistance observed in nude mice.
Conclusions:
- The study confirms that differential lesion severity between BALB/c and CBA/CaH mice during C. albicans infection is not mediated by T lymphocyte-dependent pathology.
- The findings support the hypothesis that strain-dependent tissue damage in this model is independent of the effector functions of macrophages or their precursors.
- Genetic background significantly influences the outcome of C. albicans infection even in the absence of adaptive T-cell immunity.