Mechanism of Cryptococcus meningoencephalitis

Abstract

Cryptococcus neoformans and Cryptococcus gattii are fungal pathogens that cause diseases in humans. Cryptococcal species mainly enter the body by inhalation and in most cases are eliminated by host defense mechanisms. Some cases, however, progress to pneumonia and subsequent dissemination of the infection to the central nervous system (CNS), leading to meningoencephalitis. Cryptococcus can cross the blood-brain barrier transcellularly, paracellularly and through infected phagocytes (the Trojan horse mechanism). The reason for the tropism of Cryptococcus to the CNS could be partially explained by the abundance of inositol in the brain, which causes the hyaluronic acid in fungal cells to bind to host CD44 receptors. There are differences in the clinical characteristics of C. neoformans and C. gattii. HIV infection is the most common risk factor for cryptococcosis due to C. neoformans, whereas C. gattii infection with CNS involvement is frequently found in otherwise healthy individuals exposed to plant propagules found in tropical and subtropical regions. As the virulence traits of C. neoformans contributing to CNS disease, high macrophage uptake and laccase activity are associated with the fungal burden and the rate of clearance of the infection from the brain. Recent reports suggested that the C. gattii VGII strain suppresses host immune responses in the lung and causes more lung infections than CNS diseases. Furthermore, the anti-GM-CSF autoantibodies are a risk factor for CNS infection by the C. gattii VGI strain. To understand the mechanism by which Cryptococcus causes CNS disease, it is important to consider the specific characteristics of the species and the molecular types.