Cryptococcus: from environmental saprophyte to global pathogen

Abstract

Cryptococcosis is a globally distributed invasive fungal infection that is caused by species within the genus Cryptococcus which presents substantial therapeutic challenges. Although natural human-to-human transmission has never been observed, recent work has identified multiple virulence mechanisms that enable cryptococci to infect, disseminate within and ultimately kill their human host. In this Review, we describe these recent discoveries that illustrate the intricacy of host-pathogen interactions and reveal new details about the host immune responses that either help to protect against disease or increase host susceptibility. In addition, we discuss how this improved understanding of both the host and the pathogen informs potential new avenues for therapeutic development.

Role of microglia in fungal infections of the central nervous system

“…61 CNS penetration by Cryptococcus spp occurs via a transcytosis, paracellular, and the Trojan horse pathways. 6,62 Post-mortem neuropathological examinations of patients' brains have demonstrated that C. neoformans' main virulence factor, its polysaccharide capsule which is extensively released during infection, is ingested and localizes inside of microglia. 63,64 In the periphery, the capsular polysaccharide can interfere with phagocytosis, antigen presentation, leukocyte migration and proliferation, and specific antibody responses, and can enhance HIV replication.…”

Paciente inmunocompetente con criptococosis cerebral: reporte de un caso

“…En México, C. neoformans se ha aislado en el 20.7% de las muestras de excrementos de palomas colectados en áreas urbanas, y en menor proporción en verduras, frutas y excrementos de otras aves 10 . La presentación clínica más común es pulmonar, de donde puede diseminarse por vía hematógena al SNC y causar meningoencefalitis [11][12][13] . Al viajar por el torrente sanguíneo, el hongo inhibe la respuesta inmunitaria del huésped y la producción de factor de necrosis tumoral, entre otros 14,15 .…”

Cryptococcosis in apparently immune-competent patients: taxonomy, epidemiology, pathophysiology and treatment

“…Evidence of latency exists in the finding of continuous antibody production, [11][12][13][14] molecular studies indicating that cryptococcosis presenting in Africans living in Europe was acquired many years earlier, 15,16 and in autopsy studies from patients without a history of cryptococcal disease or exposure describing pulmonary granulomas containing C. neoformans. 17,18 The ability of the fungus to persist in humans without triggering a successful immune reaction has likely evolved due to its saprophytic nature (reviewed in [7][8][9] ). For example, C. neoformans is able to survive and replicate within macrophages in a similar way to which it exists as an intracellular parasite of amoebae in the environment.…”