1. Cryptococcosis: Pathogenesis and immune response
Dr. Tihana Bicanic
Reader and Consultant in Infectious Diseases
Centre for Global Health, Institute of Infection and Immunity,
St. George’s, University of London; St George's Hospital NHS Foundation Trust

2. Intended learning outcomes
To understand the pathogenesis of cryptococcal meningitis
To be aware of the host immune response to Cryptococcus

3. Pathogenesis Environmental Yeast: soil, tree bark, avian guano
Humans are ‘universally exposed’ through inhalation
Incubation period unknown
Initial pulmonary infection usually asymptomatic leading to latency: Infection is common, disease is rare
Disease: primary or reactivation in immunocompromised (favoured)
Systemic dissemination haematogenous: CNS most common; other sites: skin, prostate, bones
Humans are a ‘dead-end host’ – no onward transmission
From Hull, C.M. and Heitman, J. Annu Rev Genet. 2002; 36:

4. Immune response and pathology
Involves both innate and adaptive immunity
(Alveolar) macrophage main effector cell
Cryptococcus phagocytosed following opsonisation (Ab and complement)
T helper cells (CD4+ T cells) activate: secrete Th1 cytokines including IFN-γ
Granulomatous response (similar to TB)
Good=cryptococcoma (intracellular)
Bad (HIV+ CD4<100)=disseminated (extracellular) infection
Cryptococci can survive, replicate within and be transmitted between macrophages- macrophages may be vehicle of dissemination to CNS

5. Summary
Cryptococcus is an environmental fungus to which we are all exposed via inhalation
Both the innate and adaptive arms of the immune system play a role in containing Cryptococcus.
Systemic dissemination occurs in patients who are immunocompromised.
CNS is the most frequent site for dissemination.

6. END