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Cryptococcosis is a prevalent fungal infection of the central nervous system (CNS) caused by Cryptococcus neoformans, a yeast with a polysaccharide capsule in the basidiomycete group. Normally, C. neoformans infects the respiratory tract and then breaches the blood–brain barrier (BBB), leading to meningitis or meningoencephalitis, which leads to hundreds of thousands of deaths each year. Although the mechanism by which C. neoformans infiltrates the BBB to invade the brain has yet to be fully understood, research has revealed that C. neoformans can cross the BBB using transcellular penetration, paracellular traversal, and infected phagocytes (the "Trojan horse" mechanism). The secretion of multiple virulence factors by C. neoformans is crucial in facilitating the spread of infection after breaching the BBB and causing brain infections. Extensive research has shown that various virulence factors play a significant role in the dissemination of infection beyond the lungs. This review explores the mechanisms of C. neoformans entering the CNS and explains how it bypasses the BBB. Additionally, it aims to understand the interplay between the regulatory mechanisms and virulence factors of C. neoformans. [ABSTRACT FROM AUTHOR]

Cryptococcosis is a prevalent fungal infection of the central nervous system (CNS) caused by Cryptococcus neoformans, a yeast with a polysaccharide capsule in the basidiomycete group. Normally, C. neoformans infects the respiratory tract and then breaches the blood–brain barrier (BBB), leading to meningitis or meningoencephalitis, which leads to hundreds of thousands of deaths each year. Although the mechanism by which C. neoformans infiltrates the BBB to invade the brain has yet to be fully understood, research has revealed that C. neoformans can cross the BBB using transcellular penetration, paracellular traversal, and infected phagocytes (the “Trojan horse” mechanism). The secretion of multiple virulence factors by C. neoformans is crucial in facilitating the spread of infection after breaching the BBB and causing brain infections. Extensive research has shown that various virulence factors play a significant role in the dissemination of infection beyond the lungs. This review explores the mechanisms of C. neoformans entering the CNS and explains how it bypasses the BBB. Additionally, it aims to understand the interplay between the regulatory mechanisms and virulence factors of C. neoformans.

Cryptococcus neoformans (C. neoformans) is a pathogenic fungus with a global distribution. Humans become infected by inhaling the fungus from the environment, and the fungus initially colonizes the lungs. If the immune system fails to contain C. neoformans in the lungs, the fungus can disseminate to the blood and invade the central nervous system, resulting in fatal meningoencephalitis particularly in immunocompromised individuals including HIV/AIDS patients. Following brain invasion, C. neoformans will encounter host defenses involving resident as well as recruited immune cells in the brain. To overcome host defenses, C. neoformans possesses multiple virulence factors capable of modulating immune responses. The outcome of the interactions between the host and C. neoformans will determine the disease progression. In this review, we describe the current understanding of how C. neoformans migrates to the brain across the blood–brain barrier, and how the host immune system responds to the invading organism in the brain. We will also discuss the virulence factors that C. neoformans uses to modulate host immune responses. [ABSTRACT FROM AUTHOR]