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Enhanced resistance against systemic Candida albicans infection in mice treated with C. albicans DNA
Petya Dimitrova1, Martin Yordanov, Svetla Danova
1Department of Immunology, Institute of Microbiology, Sofia, Bulgaria.
Abstract:
In this study, double-stranded Candida albicans DNA was administered in systemic C. albicans infection in at dose of 20 microg per mouse at 4, 5 and 6 weeks of age. The level of IL-12 in serum was elevated as a result of yeast DNA treatment and correlated with lower mortality and decreased kidney and liver injury. Macrophage activation was demonstrated by an increase of nitric oxide (NO) and IL-12 production. These effects were Janus activation kinases (JAK)/signal transducer and activator of transcription (STAT) dependent as they were inhibited by selective JAK inhibitor tyrphostin AG-490. DNA influenced adaptive immune response through elevation of anti-Candida IgG antibody production in systemic C. albicans infection. Thus, C. albicans DNA augmented innate and adaptive immune responses against the pathogen.
Insights
Double-stranded Candida albicans DNA boosts the immune system, reducing mortality and organ damage in systemic infections. This yeast DNA enhances both innate and adaptive immunity against the pathogen.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Systemic Candida albicans infections pose significant health risks.
- Understanding host immune responses to C. albicans is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the immunomodulatory effects of double-stranded Candida albicans DNA in a systemic infection model.
- To determine the impact of this DNA on innate and adaptive immune responses.
Main Methods:
- Administration of double-stranded C. albicans DNA to mice during systemic infection.
- Measurement of serum IL-12 levels, nitric oxide (NO) production, and anti-Candida IgG antibodies.
- Assessment of kidney and liver injury and animal mortality.
- Evaluation of Janus activation kinases (JAK)/signal transducer and activator of transcription (STAT) pathway involvement using a JAK inhibitor.
Main Results:
- Yeast DNA treatment elevated serum IL-12 levels, correlating with reduced mortality and organ damage.
- Macrophage activation was evidenced by increased NO and IL-12 production.
- The observed effects were dependent on the JAK/STAT pathway, as shown by inhibition with tyrphostin AG-490.
- DNA administration enhanced anti-Candida IgG antibody production, indicating a boosted adaptive immune response.
Conclusions:
- Double-stranded C. albicans DNA effectively augments both innate and adaptive immune responses against systemic C. albicans infection.
- This DNA treatment demonstrates therapeutic potential by reducing pathogen burden and associated host injury.
- The JAK/STAT pathway plays a critical role in mediating the immunomodulatory effects of C. albicans DNA.
