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A protective role of platelet-activating factor in murine candidiasis
1Department of Microbiology, College of Natural Sciences, Chonnam National University, Kwangju, Republic of Korea.
Abstract:
Platelet-activating factor (PAF) is a potent phospholipid-derived modulator of immunological and inflammatory processes. In this study, the role of exogenous and endogenous PAF in resistance to infection with Candida albicans was investigated. Administration of PAF following a lethal challenge of C. albicans significantly protected mice from death and reduced the number of organisms in the kidneys. Neutralization of endogenous PAF with the PAF antagonist BN50739 shortened the mean survival time and increased the number of C. albicans cells per kidney. Shortly after infection of mice (30 min), significant levels of PAF were detected in the serum. PAF-induced protection appears to be mediated through the actions of tumor necrosis factor alpha (TNF-alpha), since pretreatment with anti-TNF-alpha before each injection of PAF abrogated the majority of PAF-induced enhanced resistance. Administration of PAF in vivo elevated serum TNF-alpha levels and TNF-alpha mRNA expression in the kidney. Production of TNF-alpha was markedly diminished by pretreatment with the PAF antagonist BN50739 prior to infection with C. albicans. We conclude that PAF, which is produced during infection with C. albicans, plays an important role in determining the level of resistance to this infectious microorganism. This effect of PAF appears to be mediated, at least in part, through the induction of TNF-alpha.
Insights
Platelet-activating factor (PAF) enhances resistance to Candida albicans infection by boosting tumor necrosis factor alpha (TNF-alpha). This study shows PAF plays a crucial role in the immune response against fungal infections.
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Platelet-activating factor (PAF) is a key mediator in immune and inflammatory responses.
- Candida albicans is a fungal pathogen that causes infections, particularly in immunocompromised individuals.
Purpose of the Study:
- To investigate the role of exogenous and endogenous Platelet-activating factor (PAF) in host resistance against Candida albicans infection.
- To elucidate the mechanisms underlying PAF-mediated protection, focusing on the involvement of tumor necrosis factor alpha (TNF-alpha).
Main Methods:
- Mice were challenged with a lethal dose of Candida albicans, with or without exogenous PAF administration.
- PAF antagonist BN50739 was used to neutralize endogenous PAF.
- Serum and kidney samples were analyzed for PAF levels, Candida albicans burden, TNF-alpha levels, and TNF-alpha mRNA expression.
- Mice were pretreated with anti-TNF-alpha to assess its role in PAF-induced protection.
Main Results:
- Administration of PAF post-infection significantly increased survival rates and reduced fungal load in kidneys.
- Neutralization of endogenous PAF led to decreased survival and increased fungal burden.
- PAF administration elevated serum TNF-alpha levels and kidney TNF-alpha mRNA expression.
- Anti-TNF-alpha pretreatment abrogated the protective effects of PAF, indicating TNF-alpha mediation.
Conclusions:
- Endogenous PAF, produced during Candida albicans infection, is critical for determining host resistance.
- PAF-mediated protection against C. albicans is, at least in part, dependent on the induction of TNF-alpha.
- PAF represents a potential therapeutic target for managing Candida albicans infections.