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Influence of muramyl dipeptide on renal candidiasis in genetically distinct mice
G A Marquis1, M Boushira, P Russo
1Department of Microbiology and Immunology, Université de Montréal, Quebec, Canada.
Abstract:
Susceptible (DBA/2) and resistant (C57BL/6) mice were inoculated intravenously with Candida albicans to evaluate the effect of a four-day prophylaxis with muramyl dipeptide (MDP) on the renal burden of organisms during the first week after infection. In sham-treated DBA/2 mice injected with 8 x 10(4) candida cells, renal CFU (LOG10 +/- SEM) on days 1, 4 and 7 after infection were found to average 5.050 +/- 0.109, 4.882 +/- 0.133 and 5.482 +/- 0.245. In sham-treated C57BL/6 mice injected with 2 x 10(5) candida cells, renal CFU on days 1, 4 and 7 reached only 3.610 +/- 0.118, 3.404 +/- 0.107 and 4.176 +/- 0.580. MDP-treated DBA/2 mice achieved significant reduction in CFU of C. albicans on day 1 (1.3 log units) and day 4 (0.6 log unit), while MDP-treated C57BL/6 mice had significant reduction in CFU of C. albicans only on day 1 (0.6 log unit) after infection. Sham-treated mice of both strains had a 28.6 to 30% increase in kidney weights on day 4 only, a transient change not seen in MDP-treated mice. Histopathological examination on days 8, 15 and 21 after infection revealed a higher incidence of renal papillary necrosis in DBA/2 mice than C57BL/6 mice (approximately 70% vs 10%). The incidence of granulomas and of chronic interstitial inflammation was much higher in MDP-treated mice. We conclude that the genetic makeup of the host influences the potential effectiveness of MDP as a biological response modifier.
Insights
Muramyl dipeptide (MDP) prophylaxis reduced Candida albicans in susceptible mice kidneys, but host genetics influenced its effectiveness. MDP treatment also altered inflammatory responses in both resistant and susceptible mouse strains.
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Candida albicans is a common fungal pathogen causing systemic infections.
- Muramyl dipeptide (MDP) is a bacterial cell wall component known for its immunomodulatory properties.
- Host genetic background significantly impacts susceptibility and response to infections.
Purpose of the Study:
- To investigate the efficacy of muramyl dipeptide (MDP) prophylaxis against Candida albicans renal infection.
- To evaluate the influence of host genetic resistance on MDP's therapeutic effect.
- To assess MDP's impact on renal fungal burden, kidney weight, and histopathological changes.
Main Methods:
- Intravenous inoculation of susceptible (DBA/2) and resistant (C57BL/6) mice with Candida albicans.
- Four-day prophylactic treatment with muramyl dipeptide (MDP) or sham treatment.
- Quantification of renal Colony Forming Units (CFU), kidney weights, and histopathological analysis at various time points.
Main Results:
- MDP significantly reduced renal Candida albicans burden in susceptible DBA/2 mice on days 1 and 4 post-infection.
- MDP provided a significant reduction in renal Candida albicans on day 1 in resistant C57BL/6 mice.
- MDP-treated mice showed no transient increase in kidney weight observed in sham-treated controls; however, MDP increased granuloma and inflammation incidence.
Conclusions:
- The effectiveness of muramyl dipeptide (MDP) as a biological response modifier against Candida albicans renal infection is influenced by the host's genetic makeup.
- MDP demonstrates partial efficacy in reducing fungal burden, particularly in susceptible hosts.
- MDP modulates the host's inflammatory and pathological response to candidiasis, with varying effects based on genetic background.