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The role of BCG/PPD-activated macrophages in resistance against systemic candidiasis in mice
J W van 't Wout1, R Poell, R van Furth
1Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Abstract:
The main conclusions of this study are that BCG/PPD-activated macrophages, in contrast to macrophages from control mice, exhibit an increased PMA-induced production of H2O2, kill about one-third of the phagocytosed Candida albicans, and cause more than 50% inhibition of the intracellular formation of germ tubes by C. albicans. Peritoneal macrophages from mice that were colonized post-natally with C. albicans do not show increased production of H2O2 upon stimulation with PMA and the intracellular outgrowth of germ tubes is inhibited to only a limited degree. These macrophages are capable of killing about 20% of the ingested C. albicans. In vivo, the number of Candida in the kidney, spleen and liver after intravenous injection of Candida albicans is significantly lower in BCG-treated mice than in control mice. Post-natal colonization with C. albicans has only a limited effect on the outgrowth of intravenously injected C. albicans in the spleen and liver but does not influence growth in the kidney. These results indicate that acquired immunity against a systemic Candida infection involves both oxidative and non-oxidative mechanisms of intracellular killing and that these mechanisms may have different effects on the yeast and hyphal forms of C. albicans.
Insights
Bacille Calmette-Guérin (BCG)-activated macrophages enhance killing of Candida albicans through increased hydrogen peroxide production and germ tube inhibition. Acquired immunity involves both oxidative and non-oxidative mechanisms against systemic fungal infections.
Area of Science:
- Immunology
- Mycology
- Microbiology
Background:
- Systemic Candida albicans infections pose significant health risks.
- Understanding the mechanisms of acquired immunity against fungal pathogens is crucial.
- Macrophages play a key role in the host defense against Candida.
Purpose of the Study:
- To investigate the functional differences in macrophages activated by BCG/PPD versus those colonized post-natally with Candida albicans.
- To elucidate the roles of oxidative and non-oxidative mechanisms in controlling systemic Candida infections.
- To assess the impact of macrophage activation on Candida albicans killing and morphogenesis.
Main Methods:
- Peritoneal macrophages from BCG-treated and Candida-colonized mice were isolated.
- Macrophage activity was assessed by measuring PMA-induced hydrogen peroxide (H2O2) production.
- Phagocytic killing of Candida albicans and inhibition of germ tube formation were quantified.
- In vivo studies involved intravenous injection of Candida albicans into mice and enumeration of fungal burden in organs.
Main Results:
- BCG/PPD-activated macrophages showed increased PMA-induced H2O2 production and significantly inhibited Candida albicans germ tube formation.
- These activated macrophages killed approximately one-third of ingested Candida albicans.
- Macrophages from Candida-colonized mice exhibited limited H2O2 production and reduced Candida killing (approx. 20%), with only partial inhibition of germ tube outgrowth.
- In vivo, BCG-treated mice had significantly lower Candida burdens in kidneys, spleen, and liver compared to controls.
Conclusions:
- Acquired immunity against systemic Candida infection involves both oxidative and non-oxidative intracellular killing mechanisms.
- BCG-mediated activation enhances macrophage fungicidal activity through increased oxidative burst and inhibition of hyphal development.
- These mechanisms differentially affect the yeast and hyphal forms of Candida albicans, impacting systemic fungal control.