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Published on: December 19, 2014
Cryptococcus neoformans Infection in the Central Nervous System: The Battle between Host and Pathogen
Yanli Chen1, Zoe W Shi1,2, Ashley B Strickland1
1Division of Immunology, Virginia-Maryland College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20742, USA.
Abstract:
Cryptococcus neoformans (C. neoformans) is a pathogenic fungus with a global distribution. Humans become infected by inhaling the fungus from the environment, and the fungus initially colonizes the lungs. If the immune system fails to contain C. neoformans in the lungs, the fungus can disseminate to the blood and invade the central nervous system, resulting in fatal meningoencephalitis particularly in immunocompromised individuals including HIV/AIDS patients. Following brain invasion, C. neoformans will encounter host defenses involving resident as well as recruited immune cells in the brain. To overcome host defenses, C. neoformans possesses multiple virulence factors capable of modulating immune responses. The outcome of the interactions between the host and C. neoformans will determine the disease progression. In this review, we describe the current understanding of how C. neoformans migrates to the brain across the blood-brain barrier, and how the host immune system responds to the invading organism in the brain. We will also discuss the virulence factors that C. neoformans uses to modulate host immune responses.
Insights
Cryptococcus neoformans can cause fatal meningoencephalitis in immunocompromised individuals. This review explores how the fungus invades the brain and evades immune responses.
Area of Science:
- Mycology
- Immunology
- Neuroscience
Background:
- Cryptococcus neoformans is a globally distributed pathogenic fungus.
- Infection occurs via inhalation, initially colonizing the lungs.
- Dissemination to the brain can cause fatal meningoencephalitis, especially in immunocompromised individuals like HIV/AIDS patients.
Purpose of the Study:
- To review the mechanisms of Cryptococcus neoformans brain invasion.
- To describe host immune responses within the brain.
- To discuss Cryptococcus neoformans virulence factors that modulate immunity.
Main Methods:
- Literature review of current research on Cryptococcus neoformans pathogenesis.
- Analysis of host-pathogen interactions at the blood-brain barrier and within the central nervous system.
- Examination of fungal virulence factors and their roles in immune evasion.
Main Results:
- Cryptococcus neoformans possesses mechanisms to cross the blood-brain barrier.
- The brain's immune cells, both resident and recruited, respond to fungal invasion.
- Fungal virulence factors are crucial for modulating host immune responses and determining disease outcome.
Conclusions:
- Understanding Cryptococcus neoformans brain invasion and immune modulation is critical for treating cryptococcal meningoencephalitis.
- Further research into virulence factors and host-pathogen interactions can inform therapeutic strategies.
- Effective immune containment in the lungs is key to preventing systemic dissemination and fatal neurological disease.
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