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

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

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 Hull, C.M. and Heitman, J. Annu Rev Genet. 2002; 36: 557-615.

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

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.

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