PMID- 29371546 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220330 IS - 2309-608X (Electronic) IS - 2309-608X (Linking) VI - 3 IP - 2 DP - 2017 Jun 2 TI - Monocyte Phenotype and IFN-gamma-Inducible Cytokine Responses Are Associated with Cryptococcal Immune Reconstitution Inflammatory Syndrome. LID - 10.3390/jof3020028 [doi] LID - 28 AB - 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-gamma ex vivo induced a higher frequency of TNF-alpha- and IL-6-producing monocytes among those who later developed IRIS. Among participants who developed IRIS, ex vivo IFN-gamma stimulation induced higher frequencies of activated monocytes, IL-6(+), TNF-alpha(+) 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. FAU - Meya, David B AU - Meya DB AD - Infectious Diseases Institute, Makerere University, Kampala, P.O. Box 22418, Uganda. david.meya@gmail.com. AD - Dept of Medicine, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis, MN 55455, USA. david.meya@gmail.com. AD - School of Medicine, College of Health Sciences, Makerere University, Kampala, P.O. Box 7072, Uganda. david.meya@gmail.com. FAU - Okurut, Samuel AU - Okurut S AD - Research Department, Makerere University Walter Reed Project, Plot 42, Nakasero Road, Kampala, P.O. Box 1624, Uganda. sokurut@muwrp.org. FAU - Zziwa, Godfrey AU - Zziwa G AD - Research Department, Makerere University Walter Reed Project, Plot 42, Nakasero Road, Kampala, P.O. Box 1624, Uganda. gzziwa@muwrp.org. FAU - Cose, Stephen AU - Cose S AD - London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK. stephen.cose@mrcuganda.org. AD - MRC/UVRI Uganda Research Unit on AIDS, UVRI, Entebbe, Plot 51-59 Nakiwogo Road, Uganda. stephen.cose@mrcuganda.org. FAU - Bohjanen, Paul R AU - Bohjanen PR AD - Dept of Medicine, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis, MN 55455, USA. bohja001@umn.edu. FAU - Mayanja-Kizza, Harriet AU - Mayanja-Kizza H AD - School of Medicine, College of Health Sciences, Makerere University, Kampala, P.O. Box 7072, Uganda. hmk@chs.mak.ac.ug. FAU - Joloba, Moses AU - Joloba M AD - School of Biomedical Sciences, Microbiology Department, Makerere University, Kampala P.O. Box 7072, Uganda. m.joloba@gmail.com. FAU - Boulware, David R AU - Boulware DR AD - Dept of Medicine, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis, MN 55455, USA. boulw001@umn.edu. FAU - Yukari Manabe, Carol AU - Yukari Manabe C AD - Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore, MD 21218, USA. ymanabe@jhmi.edu. FAU - Wahl, Sharon AU - Wahl S AD - National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA. SMWahl@dir.nidcr.nih.gov. FAU - Janoff, Edward N AU - Janoff EN AD - Mucosal and Vaccine Research Program Colorado (MAVRC), University of Colorado Denver, Aurora, CO 80045, USA. Edward.Janoff@ucdenver.edu. LA - eng GR - U01 AI089244/AI/NIAID NIH HHS/United States GR - K24 AI096925/AI/NIAID NIH HHS/United States GR - R21 NS065713/NS/NINDS NIH HHS/United States GR - R01 AI078934/AI/NIAID NIH HHS/United States GR - T32 AI055433/AI/NIAID NIH HHS/United States GR - R01 AI108479/AI/NIAID NIH HHS/United States PT - Journal Article DEP - 20170602 PL - Switzerland TA - J Fungi (Basel) JT - Journal of fungi (Basel, Switzerland) JID - 101671827 PMC - PMC5715914 OTO - NOTNLM OT - Cryptococcus OT - HIV OT - IRIS OT - cryptococcal meningitis OT - innate immune response OT - monocytes COIS- The authors declare no conflict of interest. EDAT- 2018/01/27 06:00 MHDA- 2018/01/27 06:01 PMCR- 2017/06/02 CRDT- 2018/01/27 06:00 PHST- 2017/04/01 00:00 [received] PHST- 2017/05/11 00:00 [revised] PHST- 2017/05/27 00:00 [accepted] PHST- 2018/01/27 06:00 [entrez] PHST- 2018/01/27 06:00 [pubmed] PHST- 2018/01/27 06:01 [medline] PHST- 2017/06/02 00:00 [pmc-release] AID - jof3020028 [pii] AID - jof-03-00028 [pii] AID - 10.3390/jof3020028 [doi] PST - epublish SO - J Fungi (Basel). 2017 Jun 2;3(2):28. doi: 10.3390/jof3020028.