Monocyte phenotype and IFN-γ-inducible cytokine responses are associated with cryptococcal immune reconstitution inflammatory syndrome

David B. Meya, Samuel Okurut, Godfrey Zziwa, Stephen Cose, Paul R. Bohjanen, Harriet Mayanja-Kizza, Moses Joloba, David R. Boulware, Carol Yukari Manabe, Sharon Wahl, Edward N. Janoff

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number28
JournalJournal of Fungi
Volume3
Issue number2
DOIs
StatePublished - Jun 2017

Keywords

  • Cryptococcal meningitis
  • Cryptococcus
  • HIV
  • IRIS
  • Innate immune response
  • Monocytes

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Plant Science
  • Microbiology (medical)

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