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J. Fungi 2017, 3(2), 28; doi:10.3390/jof3020028

Monocyte Phenotype and IFN-γ-Inducible Cytokine Responses Are Associated with Cryptococcal Immune Reconstitution Inflammatory Syndrome

1
Infectious Diseases Institute, Makerere University, Kampala, P.O. Box 22418, Uganda
2
Dept of Medicine, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis, MN 55455, USA
3
School of Medicine, College of Health Sciences, Makerere University, Kampala, P.O. Box 7072, Uganda
4
Research Department, Makerere University Walter Reed Project, Plot 42, Nakasero Road, Kampala, P.O. Box 1624, Uganda
5
London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK
6
MRC/UVRI Uganda Research Unit on AIDS, UVRI, Entebbe, Plot 51-59 Nakiwogo Road, Uganda
7
School of Biomedical Sciences, Microbiology Department, Makerere University, Kampala P.O. Box 7072, Uganda
8
Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore, MD 21218, USA
9
National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA
10
Mucosal and Vaccine Research Program Colorado (MAVRC), University of Colorado Denver, Aurora, CO 80045, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Adilia Warris
Received: 1 April 2017 / Revised: 11 May 2017 / Accepted: 27 May 2017 / Published: 2 June 2017
(This article belongs to the Special Issue Host–Fungus Interactions)
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Abstract

A third of adults with AIDS and cryptococcal meningitis (CM) develop immune reconstitution inflammatory syndrome (IRIS) after initiating antiretroviral therapy (ART), which is thought to result from exaggerated inflammatory antigen-specific T cell responses. The contribution of monocytes to the immunopathogenesis of cryptococcal IRIS remains unclear. We compared monocyte subset frequencies and immune responses in HIV-infected Ugandans at time of CM diagnosis (IRIS-Baseline) for those who later developed CM-IRIS, controls who did not develop CM-IRIS (Control-Baseline) at CM-IRIS (IRIS-Event), and for controls at a time point matched for ART duration (Control-Event) to understand the association of monocyte distribution and immune responses with cryptococcal IRIS. At baseline, stimulation with IFN-γ ex vivo induced a higher frequency of TNF-α- and IL-6-producing monocytes among those who later developed IRIS. Among participants who developed IRIS, ex vivo IFN-γ stimulation induced higher frequencies of activated monocytes, IL-6+, TNF-α+ classical, and IL-6+ intermediate monocytes compared with controls. In conclusion, we have demonstrated that monocyte subset phenotype and cytokine responses prior to ART are associated with and may be predictive of CM-IRIS. Larger studies to further delineate innate immunological responses and the efficacy of immunomodulatory therapies during cryptococcal IRIS are warranted. View Full-Text
Keywords: cryptococcal meningitis; Cryptococcus; HIV; monocytes; innate immune response; IRIS cryptococcal meningitis; Cryptococcus; HIV; monocytes; innate immune response; IRIS
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MDPI and ACS Style

Meya, D.B.; Okurut, S.; Zziwa, G.; Cose, S.; Bohjanen, P.R.; Mayanja-Kizza, H.; Joloba, M.; Boulware, D.R.; Yukari Manabe, C.; Wahl, S.; Janoff, E.N. Monocyte Phenotype and IFN-γ-Inducible Cytokine Responses Are Associated with Cryptococcal Immune Reconstitution Inflammatory Syndrome. J. Fungi 2017, 3, 28.

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