Cryptococcus neoformans ex vivo capsule size is associated with intracranial pressure and host immune response in HIV-associated cryptococcal meningitis

Robertson, E.J. et al. (2014) Cryptococcus neoformans ex vivo capsule size is associated with intracranial pressure and host immune response in HIV-associated cryptococcal meningitis. Journal of Infectious Diseases, 209(1), pp. 74-82. (doi:10.1093/infdis/jit435)

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Abstract

Background. The Cryptococcus neoformans polysaccharide capsule is a well-characterised 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. 134 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(pre-treatment) 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-gamma(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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tassieri, Dr Manlio and Carlsson, Dr Allan
Authors: Robertson, E.J., Najjuka, G., Rolfes, M.A., Akampurira, A., Jain, N., Anantharanjit, J., von Hohenburg, M., Tassieri, M., Carlsson, A., Meya, D.B., Harrison, T.S., Fries, B., Boulware, D.R., and Bicanic, T.
College/School:College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Journal of Infectious Diseases
Publisher:Infectious Diseases Society of America
ISSN:0022-1899
ISSN (Online):1537-6613
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in Journal of Infectious Diseases 209(1):74-82 2013
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
534472Rheology at the Microscale: New Tools for Bio-analysisManlio TassieriEngineering & Physical Sciences Research Council (EPSRC)10216/101ENG - BIOMEDICAL ENGINEERING