Cryptococcosis pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Serge Korjian M.D.; Yazan Daaboul, M.D.

Infective cryptococcal species are ubiquitous and natural exposure by inhalation is very common. Cryptococci are intracellular pathogens. Once they are phagocytosed, they germinate and multiply within the macrophages. The immune response to cryptococcal infection is highly dependent on host T-cell function, interferon-γ and TNF-α signaling. Microscopically, Cryptococci are characterized by a thick mucopolysaccharide capsule with a refractile center.

• Infective cryptococcal species are ubiquitous and natural exposure is very common.^[1]
• Infection occurs by inhalation of aerosolized, dessicated basidiospores.^[2]

• Cryptococcus polysaccharide capsule, phospholipase activity and extracellular vesicles play key roles in the survival of the organism within the host.^[3]

• Once these spores reach the alveoli, they are phagocytosed by the alveolar macrophages without prior opsonization (usually required for yeast forms).
• Cryptococci are intracellular pathogens. Once they are phagocytosed, they germinate and multiply within the macrophages.^[4]
• Activated macrophages are capable of destroying the yeast forms that develop; however, non-activated macrophages act as germination centers for cryptococci.^[5]
• Cryptococci have the ability to form giant cells that resist phagocytosis and have been hypothesized to play a role in latent infections, and reactivation.^[5]
• Cryptococci also have the ability to change the number of sets of chromosomes they have during infection; this has been associated with heteroresistance to certain antifungal agents.^[6]

• After exposure to desiccated yeast cells or spores, patients may clear the infection, contain it within granulomata as a latent infection, or the infection may disseminate. This depends on the host’s immune status or other, less well-understood mechanisms.

• Disseminated disease occurs among patients with compromised cell-mediated immunity.
• The immune response to cryptococcal infection is highly dependent on host T-cell function, interferon-γ and TNF-α signaling.
• Granuloma formation can be seen and may also be responsible for reactivation in patients presenting with immunocompromised states.^[7][8]

• Cryptococcus exists in yeast form.
• It is round/ovoid and approximately 5-15 μm (resembles Histoplasma or Candida, but often larger).
• It is characterized by a thick mucopolysaccharide capsule with a refractile center.
• India ink staining is used for easy visualization of the capsule in cerebrospinal fluid.^[9]
• It has a tear drop-shaped budding pattern which is useful for differentiating Cryptococcus from Blastomyces and Histoplasma.
• Cryptococcal infections are usually accompanied by very little inflammation.
• Cryptococcus stain positive with methenamine silver, Alcian blue, and PAS (may be confused with corpora amylacea in the CNS).^[10]

{{#ev:youtube|ZG0AcmtBLe4}}