Abstract
Cryptococcus species are environmental fungal pathogens and the causative agents of cryptococcosis. Infection occurs upon inhalation of infectious particles, which proliferate in the lung causing a primary infection. From this primary lung infection, fungal cells can eventually disseminate to other organs, particularly the brain, causing lethal meningoencephalitis. However, in most cases, the primary infection resolves with the formation of a lung granuloma. Upon severe immunodeficiency, dormant cryptococcal cells will start proliferating in the lung granuloma and eventually will disseminate to the brain. Many investigators have sought to study the protective host immune response to this pathogen in search of host parameters that keep the proliferation of cryptococcal cells under control. The majority of the work assimilates research carried out using the primary infection animal model, mainly because a reactivation model has been available only very recently. This review will focus on anti-cryptococcal immunity in both the primary and reactivation models. An understanding of the differences in host immunity between the primary and reactivation models will help to define the key host parameters that control the infections and are important for the research and development of new therapeutic and vaccine strategies against cryptococcosis.
Highlights
CRYPTOCOCCUS NEOFORMANS IS AN OPPORTUNISTIC FUNGAL PATHOGENCryptococcus spp. are basidiomycetes ubiquitously found within the environment as basidiospores and budding yeast, most commonly in the soil, trees, and avian habitations [1, 2]
Studies in our lab found that when mice are infected with a C. neoformans mutant strain in which the glucosylceramide synthase gene has been deleted, they formed lung granulomas that closely resembled human lung granulomas [111]
With the ever-increasing population of immunocompromised individuals, improvements in treatment and vaccinations are imperative for opportunistic infections, such as cryptococcosis
Summary
Cryptococcus spp. are basidiomycetes ubiquitously found within the environment as basidiospores and budding yeast, most commonly in the soil, trees, and avian habitations [1, 2]. The Cryptococcus neoformans/gattii species complex has a high degree of heterogeneity, and has been classified by numerous molecular typing techniques [8, 9] These genotypic classifications have greatly aided in the epidemiology and genetic diversity that exists within these species, the serotype classification of these species will be most relevant to this review since our focus is on the host immune response to the yeast. Spores can evade host immunity much more efficiently than yeast cells, causing the development of a latent infection, and perhaps, they may represent a better model for studying the reactivation model It is not known if spores are able to promote granuloma formation in mice and represents a topic for future investigation
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