Parasitism of macrophages facilitate replication and may also facilitate migration of yeast to the central nervous system (CNS).
Cryptococci eventually exit the macrophage through cell lysis, actin-dependent direct cell-to-cell transfer, or non–lytic exocytosis.
Download jarvis mark 3 alpha free#
However, in some circumstances and in the absence of appropriate macrophage activation, cryptococci can survive and replicate within the phagolysosome, protected through a variety of mechanisms, including expansion of its thick polysaccharide capsule and laccase-induced melanin synthesis that may neutralize free radicals. Once internalized, yeast-containing phagosomes fuse with lysosomes, and intracellular killing may occur under the influence of interferon-γ (IFN-γ) produced by natural killer cells and CD4 T cells. Phagocytosis occurs through antibody- and complement-mediated, opsonin-dependent pathways and non-opsonin-dependent interaction of cryptococcus surface epitopes with receptors including mannose, dectin-1, CD14, and Toll-like receptor 4. What is the normal host immune response to Cryptococcus?Īlveolar macrophages constitute a primary first-line host defense and recognize Cryptococcus spores via Dectin-1 receptors. If the host immune response is impaired, however, yeasts may survive and disseminate through the body hematogenously, resulting in a severe meningoencephalitis ( Fig 1). The host immune response leads to clearance of infection or to latent infection with yeast encased within pulmonary granulomata. Following inhalation of spores or desiccated yeast cells, an asymptomatic pulmonary infection occurs in the vast majority of immunocompetent hosts, with detectable antibody responses to Cryptococcus protein extract by early childhood. gattii, a related organism with a more limited geographic distribution but with the capacity to cause disease in nonimmunocompromised hosts. It is primarily caused by infection with Cryptococcus neoformans, an encapsulated yeast found widely in the environment. Cryptococcal meningitis (CM) is the leading cause of meningitis in much of sub-Saharan Africa, where it causes up to 20% of all deaths in human immunodeficiency virus (HIV)-infected cohorts.