The @entity1 fungal pathogen @entity1327 is capable of infecting a broad range of hosts, from invertebrates like amoebas and @entity2199 to standard vertebrate models such as @entity19 and @entity95 . Here we have taken advantage of a @entity3392 model to investigate host-pathogen interactions of @entity1327 with the @entity3392 innate immune system, which shares a highly conserved framework with that of mammals. Through live-imaging observations and genetic knockdown, we establish that macrophages are the primary immune cells responsible for responding to and containing acute @entity281 . By interrogating survival and cryptococcal burden following @entity281 with a panel of @entity1327 mutants, we find that virulence factors initially identified as important in causing disease in @entity19 are also necessary for pathogenesis in @entity3392 larvae. Live imaging of the cranial blood vessels of infected larvae reveals that @entity1327 is able to penetrate the @entity3392 brain following intravenous @entity281 . By studying a @entity1327 FNX1 gene mutant, we find that blood-brain barrier invasion is dependent on a known cryptococcal invasion-promoting pathway previously identified in a @entity19 model of central nervous system invasion. The @entity3392 - @entity1327 platform provides a visually and genetically accessible vertebrate model system for cryptococcal pathogenesis with many of the advantages of small invertebrates. This model is well suited for higher-throughput screening of mutants, mechanistic dissection of cryptococcal pathogenesis in live animals, and use in the evaluation of therapeutic agents. IMPORTANCE: @entity1327 is an important opportunistic pathogen that is estimated to be responsible for more than 600,000 @entity204 worldwide annually. Existing @entity1 models of cryptococcal pathogenesis are costly, and the analysis of important pathogenic processes such as @entity693 is laborious and remains a challenge to visualize. Conversely, although invertebrate models of @entity281 allow high-throughput assays, they fail to replicate the anatomical complexity found in vertebrates and, specifically, cryptococcal stages of disease. Here we have utilized larval @entity3392 as a platform that overcomes many of these limitations. We demonstrate that the pathogenesis of @entity1327 @entity281 in @entity3392 involves factors identical to those in @entity1 and invertebrate infections. We then utilize the live-imaging capacity of @entity3392 larvae to follow the progression of @entity281 in real time and establish a relevant model of the @entity4767 phase of disease in a nonmammalian model.

Live Imaging of Host-Parasite Interactions in a XXXX Infection Model Reveals Cryptococcal Determinants of Virulence and Central Nervous System Invasion.

@entity1 :: ('9606', 'Species') :: ['mammalian', 'human'] @entity4767 :: ('MESH:D002494', 'Disease') :: ['critical central nervous system infection'] @entity2199 :: ('6239', 'Species') :: ['nematodes'] @entity19 :: ('10090', 'Species') :: ['mice', 'murine'] @entity1327 :: ('5207', 'Species') :: ['Cryptococcus', 'C.  neoformans', 'Cryptococcus neoformans'] @entity95 :: ('9986', 'Species') :: ['rabbits'] @entity693 :: ('MESH:D008581', 'Disease') :: ['meningitis'] @entity281 :: ('MESH:D007239', 'Disease') :: ['cryptococcal infection', 'cryptococcal infections', 'infection'] @entity204 :: ('MESH:D003643', 'Disease') :: ['deaths'] @entity3392 :: ('7955', 'Species') :: ['zebrafish']
@entity3392 :: (7955,Species) :: ['Zebrafish']
