Associations between Cryptococcus Genotypes, Phenotypes, and Clinical Parameters of Human Disease: A Review

Abstract

The genus Cryptococcus contains two primary species complexes that are significant opportunistic human fungal pathogens: C. neoformans and C. gattii. In humans, cryptococcosis can manifest in many ways, but most often results in either pulmonary or central nervous system disease. Patients with cryptococcosis can display a variety of symptoms on a spectrum of severity because of the interaction between yeast and host. The bulk of our knowledge regarding Cryptococcus and the mechanisms of disease stem from in vitro experiments and in vivo animal models that make a fair attempt, but do not recapitulate the conditions inside the human host. To better understand the dynamics of initiation and progression in cryptococcal disease, it is important to study the genetic and phenotypic differences in the context of human infection to identify the human and fungal risk factors that contribute to pathogenesis and poor clinical outcomes. In this review, we summarize the current understanding of the different clinical presentations and health outcomes that are associated with pathogenicity and virulence of cryptococcal strains with respect to specific genotypes and phenotypes.

Cryptococcus neoformans Δsgl1 Vaccination Requires Either CD4+ or CD8+ T Cells for Complete Host Protection

“…These SGs were believed to cause the significantly increased levels of Th1 cytokines, including IL-1α, TNFα, IL-17, and IFNγ, and decreased levels of Th2 cytokines, including IL-4 and IL-5 ( Figure 2 ) since they occurred over the same timeline as the SGs were measurable in vivo ( Figure 1C ). It is widely accepted that host protection against C. neoformans requires a pro-inflammatory type 1 immune response mediated by IFNγ ( Mourad and Perfect, 2018 ; Li et al., 2019 ; Linyu et al., 2020 ; Hester et al., 2020 ; Normile et al., 2020a ; Akhtar et al., 2020 ; Montoya et al., 2021 ). Interestingly, SGs have been shown to induce Th1 T cell polarization ( Bouic et al., 1996 ; Lee and Han, 2006 ; Lee et al., 2007 ), but these studies have used plant-based SGs, not fungal-derived SGs.…”

“…Given the rise in lymphopenia due to HIV/AIDS, solid organ transplant, chemotherapy ( Li et al., 2019 ; Fierer, 2019 ; Pathakumari et al., 2020 ), and immunosuppressive therapies to control chronic diseases ( Grebenciucova et al., 2016 ; Ward et al., 2016 ; Bryan et al., 2020 ), opportunistic invasive fungal infections have emerged as a global health concern, killing ~1.5 million people per year. Among these opportunistic fungal infections, cryptococcosis is caused by Cryptococcus neoformans and Cryptococcus gattii ( Chang and Chen, 2015 ; Diaz, 2020 ; Montoya et al., 2021 ), resulting in ~220,000 new cases and ~180,000 deaths annually ( Rajasingham et al., 2017 ; Mayer and Kronstad, 2020 ).…”

Cryptococcal meningitis in an immunocompetent individual: A case report

“…neoformans is primarily observed in European countries and C . gattii has historically been geographically restricted to tropical and subtropical regions, such as southern California, Hawaii, Vancouver Island, and the Pacific Northwest region, Brazil, Australia, Southeast Asia, and central Africa 10,11 . The species other than C .…”

Multiplex PCR - RFLP Assay for Identification of Cryptococcus neoformans and Cryptococcus gattii Isolated from Birds’ Droppings and Eucalyptus Trees

“…This disease is mainly caused by encapsulated basidiomycetous yeasts C. neoformans/C. gattii species complex [3,4]. Cryptococcosis is also very important in a wide range of animals worldwide as cats, dogs, horses, cattle, sheep, goats, and birds.…”

“…This disease is mainly caused by encapsulated basidiomycetous yeasts C. neoformans/C. gattii species complex [3,4].…”