What are the two major human-pathogenic Cryptococcus species?
- Cryptococcus neoformans
- Cryptococcus gattii
These species are significant causes of cryptococcal infections.
What type of polysaccharide capsule does Cryptococcus have?
A thick glucuronoxylomannan (GXM) capsule
This capsule is a key virulence factor and is strongly anti-phagocytic.
Why is the Cryptococcus capsule important for immune evasion?
- Prevents phagocytosis
- Masks underlying PAMPs (β-glucan, mannans)
- Suppresses immune responses
- Resists complement
The capsule plays a crucial role in avoiding the host’s immune system.
Which form is typical in host tissue: yeast or hyphae?
Yeast (encapsulated)
The yeast form is the pathogenic form found in infected tissues.
What is the primary environmental source of C. neoformans?
Pigeon droppings (nitrogen-rich environments)
These environments provide the necessary nutrients for the fungus.
What disease is characteristic of Cryptococcus infection?
Cryptococcal meningitis
This condition is a severe complication of cryptococcal infection.
Who is most at risk of cryptococcal meningitis?
- HIV/AIDS patients with low CD4⁺ T cell counts
- Organ transplant recipients
- Patients on immunosuppressive therapy
These groups have weakened immune systems, making them more susceptible.
How does Cryptococcus enter the body?
Inhalation of desiccated yeast/basidiospores → lungs → bloodstream → brain
This pathway illustrates the route of infection.
Why does Cryptococcus have strong neurotropism?
- CNS has low complement levels
- Rich in catecholamines, which Cryptococcus can use for melanin synthesis
- Immune-privileged environment
These factors contribute to its ability to infect the central nervous system.
What is melanin’s role in Cryptococcus virulence?
- Synthesised by laccase
- Protects fungus from oxidative stress
- Enhances survival inside macrophages
Melanin contributes to the pathogen’s ability to withstand host defenses.
How does Cryptococcus survive inside macrophages?
- Prevents phagolysosomal maturation
- Neutralises ROS
- Capsule and melanin reduce killing
- Can replicate intracellularly
These mechanisms allow Cryptococcus to evade destruction by immune cells.
What is vomocytosis?
Non-lytic expulsion of Cryptococcus from macrophages
This process allows the fungus to escape while keeping the host cell alive.
Why is vomocytosis advantageous for the fungus?
- Avoids immune detection
- Allows intracellular transport then escape into tissues
- Helps cross blood-brain barrier
This strategy enhances the pathogen’s ability to spread and survive.
What are Titan cells?
- Enlarged yeast cells (20–100 µm)
- Thick capsule
- Polyploid
Titan cells are a unique form of Cryptococcus that contribute to its virulence.
Why are Titan cells important in virulence?
- Too large for phagocytosis
- Resist oxidative stress
- Produce smaller progeny that are more infectious
- Promote immune evasion and chronic infection
Their size and characteristics enhance the fungus’s ability to evade the immune system.
Which immune cells are most important for controlling Cryptococcus?
- Th1 CD4⁺ T cells (IFN-γ)
- Activated macrophages
- NK cells
These cells play a crucial role in the immune response against Cryptococcus.
Which immune response is most protective: Th1, Th2, or Th17?
Th1 (IFN-γ → activates macrophages)
Th1 responses are critical for effective antifungal immunity.
Why is Th2 immunity detrimental in cryptococcosis?
- Produces IL-4/IL-13 → alternative macrophage activation
- Less fungicidal activity
- Worse outcomes
Th2 responses can hinder effective clearance of the infection.
How does Cryptococcus cross the blood-brain barrier?
- Trojan horse via macrophages
- Transcytosis across endothelial cells
- Paracellular migration
These mechanisms facilitate the fungus’s entry into the central nervous system.
Which diagnostic tests are used for cryptococcal disease?
- Cryptococcal antigen test (CrAg, very sensitive)
- India ink stain (CSF)
- Fungal culture
These tests are essential for diagnosing cryptococcal infections.
What is the most common presentation of cryptococcal meningitis?
- Headache
- Fever
- Neck stiffness (less common than bacterial meningitis)
- Raised intracranial pressure
- Mental status changes
These symptoms are indicative of cryptococcal meningitis.
What drug is used for initial (induction) therapy?
Amphotericin B + flucytosine
This combination is often used to treat severe cryptococcal infections.
What drug is used for long-term maintenance therapy?
Fluconazole (for months)
Long-term therapy is necessary to prevent relapse.
What is the mortality rate of cryptococcal meningitis in HIV patients?
Up to ~40% despite treatment
This high mortality rate highlights the severity of the infection.
