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Cryptococcus neoformans Ex Vivo Capsule Size Is Associated With Intracranial Pressure and Host Immune Response in HIV-associated Cryptococcal Meningitis

Year: 2013
Type: article
Study design: Observational Study
Abstract: 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.
DOI: 10.1093/infdis/jit435
Authors: Emma J. Robertson, Grace Najjuka, Melissa A. Rolfes, Andrew Akampurira, Neena Jain, Janani Anantharanjit, Maximilian von Hohenberg, Manlio Tassieri, Allan Carlsson, David B. Meya, Thomas S. Harrison, Bettina C. Fries, David R. Boulware, Tihana Bicanic
Institutions: St George's, University of London, Infectious Diseases Institute, Makerere University, University of Minnesota, Albert Einstein College of Medicine, University of Glasgow
Language: English
Subfield: Epidemiology
Field: Medicine
Open Access status: hybrid
Estimated APC paid: $4,763
Funders: Wellcome Trust, Royal Academy of Engineering, National Institutes of Health, Center for AIDS Research, University of Washington, Engineering and Physical Sciences Research Council, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke
Awards: G1925748620, G215161237, G3176921459, Center for AIDS Research (CFAR), G4406226921, Impact of HIV and HIV therapy on the Etiology and Outcome of Meningitis in Uganda, Wellcome Trust Bloomsbury Centre for Global Health Research., The impact of C neoformans phenotype and genotype on the clinical course and outcome of human cryptococcal meningitis., G7569134466, G9000121821, G9000138926, G9000165061, G9000262895
OpenAlex ID: W2118961831
FWCI: 6.913
Cites: 44
Cited by: 114
Related to: 10