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Updated: Jul 11, 2026
Th17 Inflammation Model of Oropharyngeal Candidiasis in Immunodeficient Mice
Published on: February 18, 2015
CpG oligodeoxynucleotides protect mice from lethal challenge with Candida albicans via a pathway involving tumor
Jung-Hwa Choi1, Hyun-Mi Ko, Sung Jun Park
1Department of Biological Sciences, College of Natural Sciences, Chonnam National University, Kwangju, Korea.
Abstract:
In this study, we have attempted to determine whether the systemic administration of CpG oligodeoxynucleotide (CpG-ODN) 1826 would protect mice against systemic lethal Candida albicans infection. CpG-ODNs were found completely to protect mice from death and also reduced the growth of C. albicans in the kidneys. The administration of CpG-ODNs resulted in early interleukin (IL)-12 mRNA expression in the kidneys and an increase in serum IL-12 levels. The protective activity of CpG-ODN was abolished in IL-12-deficient (IL-12-/-) mice, thereby indicating the IL-12-dependency inherent to the effects of CpG-ODN. The protective effect of CpG-ODN was not associated with the activity of NF-kappaB. Interestingly, in tumor necrosis factor (TNF)-alpha-deficient (TNF-/-) mice CpG-ODN neither exerted protective effects nor induced IL-12 expression. These data indicate that CpG-ODN protects animals against lethal C. albicans challenge via a pathway that involves the TNF-alpha-dependent induction of IL-12.
Insights
CpG oligodeoxynucleotide (CpG-ODN) 1826 completely protected mice against lethal Candida albicans infection by inducing interleukin-12 (IL-12) in a pathway involving tumor necrosis factor-alpha (TNF-alpha). This finding highlights a novel therapeutic strategy for invasive fungal infections.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Systemic Candida albicans infection poses a significant threat, necessitating novel therapeutic interventions.
- CpG oligodeoxynucleotides (CpG-ODN) are known immune modulators with potential antimicrobial applications.
Purpose of the Study:
- To investigate the protective efficacy of CpG-ODN 1826 against systemic lethal Candida albicans infection in a murine model.
- To elucidate the underlying immunological mechanisms, particularly the roles of IL-12 and TNF-alpha, in CpG-ODN-mediated protection.
Main Methods:
- Systemic administration of CpG-ODN 1826 to mice challenged with a lethal dose of Candida albicans.
- Assessment of survival rates, fungal burden in kidneys, and expression of IL-12 mRNA and serum IL-12 levels.
- Evaluation of CpG-ODN efficacy and IL-12 induction in IL-12-deficient and TNF-alpha-deficient mice.
Main Results:
- CpG-ODN 1826 conferred complete protection against lethal Candida albicans infection and reduced fungal growth in kidneys.
- CpG-ODN administration led to early IL-12 mRNA expression and increased serum IL-12 levels.
- Protective effects and IL-12 induction were abolished in IL-12-deficient mice, confirming IL-12 dependency.
- CpG-ODN failed to protect or induce IL-12 in TNF-alpha-deficient mice, indicating a crucial role for TNF-alpha.
Conclusions:
- CpG-ODN 1826 provides significant protection against systemic lethal Candida albicans infection in mice.
- The protective mechanism is dependent on the induction of IL-12, which is itself regulated by TNF-alpha.
- CpG-ODN represents a promising immunotherapeutic agent for invasive candidiasis, acting via a TNF-alpha-dependent IL-12 pathway.
