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Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans
Published on: December 19, 2014
Cryptococcus and Phagocytes: Complex Interactions that Influence Disease Outcome
Chrissy M Leopold Wager1, Camaron R Hole1, Karen L Wozniak1
1Department of Biology, The University of Texas at San AntonioSan Antonio, TX, USA; The South Texas Center for Emerging Infectious Diseases, The University of Texas at San AntonioSan Antonio, TX, USA.
Abstract:
Cryptococcus neoformans and C. gattii are fungal pathogens that cause life-threatening disease. These fungi commonly enter their host via inhalation into the lungs where they encounter resident phagocytes, including macrophages and dendritic cells, whose response has a pronounced impact on the outcome of disease. Cryptococcus has complex interactions with the resident and infiltrating innate immune cells that, ideally, result in destruction of the yeast. These phagocytic cells have pattern recognition receptors that allow recognition of specific cryptococcal cell wall and capsule components. However, Cryptococcus possesses several virulence factors including a polysaccharide capsule, melanin production and secretion of various enzymes that aid in evasion of the immune system or enhance its ability to thrive within the phagocyte. This review focuses on the intricate interactions between the cryptococci and innate phagocytic cells including discussion of manipulation and evasion strategies used by Cryptococcus, anti-cryptococcal responses by the phagocytes and approaches for targeting phagocytes for the development of novel immunotherapeutics.
Insights
Cryptococcus fungi cause severe lung infections by evading immune cells like macrophages. Understanding these interactions is key to developing new antifungal immunotherapies.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Cryptococcus neoformans and Cryptococcus gattii are fungal pathogens causing life-threatening diseases, primarily through inhalation into the lungs.
- Phagocytes, such as macrophages and dendritic cells, are crucial innate immune cells that encounter these fungi in the lungs, significantly influencing disease outcomes.
- Cryptococcus employs virulence factors like a polysaccharide capsule and melanin to evade immune responses and survive within phagocytes.
Purpose of the Study:
- To review the complex interactions between Cryptococcus species and innate phagocytic cells.
- To explore Cryptococcus's manipulation and evasion strategies against host immune cells.
- To discuss anti-fungal responses by phagocytes and potential immunotherapeutic targets.
Main Methods:
- This review synthesizes existing literature on Cryptococcus-phagocyte interactions.
- It analyzes the mechanisms of immune evasion employed by Cryptococcus.
- It examines the anti-cryptococcal activities of phagocytes and potential therapeutic strategies.
Main Results:
- Cryptococcus utilizes virulence factors to subvert phagocyte functions and evade immune detection.
- Phagocytes mount responses to control fungal growth, but these can be overcome by Cryptococcus.
- Understanding these intricate interactions reveals opportunities for novel immunotherapeutic interventions.
Conclusions:
- Targeting phagocyte responses offers a promising avenue for developing new treatments against Cryptococcus infections.
- Further research into Cryptococcus-phagocyte dynamics can lead to improved therapeutic strategies.
- Manipulating host immunity presents a viable approach to combat life-threatening fungal diseases.
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