title: How Cryptococcus interacts with the blood-brain barrier.
abstract: Cryptococcus demonstrates predilection for invasion of the brain, but the mechanism by which Cryptococcus crosses the blood-brain barrier (BBB) to cause brain invasion is largely unknown. In order for Cryptococcus to cross the BBB, there must be a way to either cross human brain microvascular endothelial cells, which are the main constitute of the BBB, or go in between tight junctions. Recent evidence of human brain microvascular endothelial cell responses to transcellular brain invasions includes membrane rearrangements, intracellular signaling pathways and cytoskeletal activations. Several Cryptococcal genes related to the traversal of BBB have been identified, including CPS1, ITR1a, ITR3c, PLB1, MPR1, FNX1 and RUB1. In addition, Cryptococcus neoformans-derived microvesicles may contribute to cryptococcal brain invasion. Paracellularly, Cryptococcus may traverse across BBB using either routes utilizing plasmin, ammonia or macrophages in a Trojan horse mechanism.
authors.affiliation: Department of Medicine, MacKay Medical College, No. 46, Sec. 3, Zhongzheng Road, Sanzhi Distric, New Taipei City 25245, Taiwan.|Division of Infectious Diseases, Department of Internal Medicine, MacKay Memorial Hospital, Taipei Branch, No. 92, Sec. 2, Zhongshan North Road, Taipei City 10449, Taiwan.|Microbiology Section, Department of Medical Research, MacKay Memorial Hospital, Tamshui Branch, No. 45, Minsheng Road, Tamshui District, New Taipei City 25160, Taiwan.
authors.forename: Hsiang-Kuang
authors.initials: HK
authors.lastname: Tseng
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, MacKay Memorial Hospital, Taipei Branch, No. 92, Sec. 2, Zhongshan North Road, Taipei City 10449, Taiwan.
authors.forename: Tseng-Yu
authors.initials: TY
authors.lastname: Huang
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, MacKay Memorial Hospital, Taipei Branch, No. 92, Sec. 2, Zhongshan North Road, Taipei City 10449, Taiwan.
authors.forename: Alice Ying-Jung
authors.initials: AY
authors.lastname: Wu
authors.affiliation: Microbiology Section, Department of Medical Research, MacKay Memorial Hospital, Tamshui Branch, No. 45, Minsheng Road, Tamshui District, New Taipei City 25160, Taiwan.
authors.forename: Hsin-Hong
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Department of Medicine, MacKay Medical College, No. 46, Sec. 3, Zhongzheng Road, Sanzhi Distric, New Taipei City 25245, Taiwan.|Division of Infectious Diseases, Department of Internal Medicine, MacKay Memorial Hospital, Taipei Branch, No. 92, Sec. 2, Zhongshan North Road, Taipei City 10449, Taiwan.|Microbiology Section, Department of Medical Research, MacKay Memorial Hospital, Tamshui Branch, No. 45, Minsheng Road, Tamshui District, New Taipei City 25160, Taiwan.
authors.forename: Chang-Pan
authors.initials: CP
authors.lastname: Liu
authors.affiliation: Hematology-Oncology/BMT, Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
authors.forename: Ambrose
authors.initials: A
authors.lastname: Jong
mesh_terms: D000641:Ammonia / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000382:microbiology*; D001921:Brain / Q000098:blood supply* / Q000382:microbiology; D003453:Cryptococcosis / Q000453:epidemiology / Q000382:microbiology / Q000473:pathology*; D003454:Cryptococcus / Q000472:pathogenicity*; D042783:Endothelial Cells / Q000382:microbiology; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008264:Macrophages / Q000382:microbiology
chemical_list: D018960:Hyaluronan Receptors; D000641:Ammonia; D005341:Fibrinolysin
keywords: Cryptococcus; blood–brain barrier; brain microvascular endothelial cell; microvesicle