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The CSF immune response in HIV-1-associated cryptococcal meningitis: macrophage activation, correlates of disease severity and effect of antiretroviral therapy.

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Scriven, James, Graham, Lisa M, Schutz, Charlotte, Scriba, Thomas J, Wilkinson, Katalin A, Wilkinson, Robert J, Boulware, David R, Urban, Britta ORCID: https://orcid.org/0000-0002-4197-8393, Meintjes, Graeme and Lalloo, David ORCID: https://orcid.org/0000-0001-7680-2200 (2017) 'The CSF immune response in HIV-1-associated cryptococcal meningitis: macrophage activation, correlates of disease severity and effect of antiretroviral therapy.'. JAIDS: Journal of Acquired Immune Deficiency Syndromes, Vol 75, Issue 3, pp. 299-307.

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Abstract

Immune modulation may improve outcome in HIV-associated cryptococcal meningitis. Animal studies suggest alternatively activated macrophages are detrimental but human studies are limited. We performed a detailed assessment of the cerebrospinal fluid (CSF) immune response and examined immune correlates of disease severity and poor outcome, and the effects of antiretroviral therapy (ART). We enrolled persons ≥18 years with first episode of HIV-associated cryptococcal meningitis. CSF immune response was assessed using flow cytometry and multiplex cytokine analysis. Principal component analysis was used to examine relationships between immune response, fungal burden, intracranial pressure and mortality, and the effects of recent ART initiation (<12 weeks). CSF was available from 57 persons (median CD4 34/μL). CD206 (alternatively activated macrophage marker) was expressed on 54% CD14+ and 35% CD14- monocyte-macrophages. High fungal burden was not associated with CD206 expression but with a paucity of CD4+, CD8+ and CD4-CD8- T cells and lower IL-6, G-CSF and IL-5 concentrations. High intracranial pressure (≥30cmH2O) was associated with fewer T cells, a higher fungal burden and larger Cryptococcus organisms. Mortality was associated with reduced interferon-gamma concentrations and CD4-CD8- T cells but lost statistical significance when adjusted for multiple comparisons. Recent ART was associated with increased CSF CD4/CD8 ratio and a significantly increased macrophage expression of CD206. Paucity of CSF T cell infiltrate rather than alternative macrophage activation was associated with severe disease in HIV-associated cryptococcosis. ART had a pronounced effect on the immune response at the site of disease.

Item Type: Article
Subjects: QW Microbiology and Immunology > Immunity by Type > QW 568 Cellular immunity. Immunologic cytotoxicity. Immunocompetence. Immunologic factors (General)
WB Practice of Medicine > Therapeutics > WB 377 Spinal, cisternal and ventricular puncture
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503.5 Complications
WL Nervous System > WL 200 Meninges. Blood-brain barrier
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Clinical Sciences & International Health > International Public Health Department
Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1097/QAI.0000000000001382
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 21 Apr 2017 08:59
Last Modified: 20 Nov 2017 13:40
URI: http://archive.lstmed.ac.uk/id/eprint/6990

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