Cryptococcus neoformans ex vivo capsule size is associated with intracranial pressure and host immune response in HIV-associated cryptococcal meningitis.
Background: The Cryptococcus neoformans polysaccharide capsule is a well-characterized virulence factor with immunomodulatory properties. The organism and/or shed capsule is postulated to raise intracranial pressure (ICP) in cryptococcal meningitis (CM) by mechanical obstruction of cerebrospinal flu...
| Publicado en: | Journal of Infectious Diseases Vol. 209; no. 1; pp. 74 - 83 |
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| Autores principales: | , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Oxford University Press / USA
Jan2014
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=103998597&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 103998597 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00221899 1YU jtl: Journal of Infectious Diseases issn: 00221899 maglogo: N pubinfo: dt: Jan2014 vid: 209 iid: 1 pid: 622 pub: Oxford University Press / USA artinfo: ui: 103998597 NLM23945372 2012437820 10.1093/infdis/jit435 NLM23945372 PMC3864387 103998597 ppf: 74 ppct: 9 formats: tig: atl: Cryptococcus neoformans ex vivo capsule size is associated with intracranial pressure and host immune response in HIV-associated cryptococcal meningitis. aug: au: Robertson, Emma J Najjuka, Grace Rolfes, Melissa A Akampurira, Andrew Jain, Neena Anantharanjit, Janani von Hohenberg, Maximilian Tassieri, Manlio Carlsson, Allan Meya, David B Harrison, Thomas S Fries, Bettina C Boulware, David R Bicanic, Tihana affil: Department of Infection and Immunity, St George's University of London, London, United Kingdom. sug: subj: AIDS-Related Opportunistic Infections Microbiology Cryptococcus Cryptococcus Immunology Fungi Immunology Meningitis, Cryptococcal Microbiology AIDS-Related Opportunistic Infections Cerebrospinal Fluid AIDS-Related Opportunistic Infections Immunology Adult Analysis of Variance Antifungal Agents Pharmacodynamics Cerebrospinal Fluid Cerebrospinal Fluid Microbiology Cytokines Female Fungi Human Intracranial Pressure Immunology Male Meningitis, Cryptococcal Cerebrospinal Fluid Meningitis, Cryptococcal Immunology Phenotype Polysaccharides Uganda Viscosity Adult: 19-44 years Female Male ab: Background: The Cryptococcus neoformans polysaccharide capsule is a well-characterized virulence factor with immunomodulatory properties. The organism and/or shed capsule is postulated to raise intracranial pressure (ICP) in cryptococcal meningitis (CM) by mechanical obstruction of cerebrospinal fluid (CSF) outflow. Little is known regarding capsule phenotype in human cryptococcosis. We investigated the relationship of ex vivo CSF capsular phenotype with ICP and CSF immune response, as well as in vitro phenotype.Methods: In total, 134 human immunodeficiency virus (HIV)-infected Ugandan adults with CM had serial lumbar punctures with measurement of CSF opening pressures, quantitative cultures, ex vivo capsule size and shedding, viscosity, and CSF cytokines; 108 had complete data. Induced capsular size and shedding were measured in vitro for 48 C. neoformans isolates.Results: Cryptococcal strains producing larger ex vivo capsules in the baseline (pretreatment) CSF correlated with higher ICP (P = .02), slower rate of fungal clearance (P = .02), and paucity of CSF inflammation, including decreased CSF white blood cell (WBC) count (P < .001), interleukin (IL)-4 (P = .02), IL-6 (P = .01), IL-7 (P = .04), IL-8 (P = .03), and interferon γ (P = .03). CSF capsule shedding did not correlate with ICP. On multivariable analysis, capsule size remained independently associated with ICP. Ex vivo capsular size and shedding did not correlate with that of the same isolates grown in vitro.Conclusions: Cryptococcal capsule size ex vivo is an important contributor to virulence in human cryptococcal meningitis. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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