PMID- 25492918 OWN - NLM STAT- MEDLINE DCOM- 20150626 LR - 20230709 IS - 1537-6613 (Electronic) IS - 0022-1899 (Print) IS - 0022-1899 (Linking) VI - 211 IP - 10 DP - 2015 May 15 TI - Cellular immune activation in cerebrospinal fluid from ugandans with cryptococcal meningitis and immune reconstitution inflammatory syndrome. PG - 1597-606 LID - 10.1093/infdis/jiu664 [doi] AB - BACKGROUND: Human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM) is characterized by high fungal burden and limited leukocyte trafficking to cerebrospinal fluid (CSF). The immunopathogenesis of CM immune reconstitution inflammatory syndrome (IRIS) after initiation of antiretroviral therapy at the site of infection is poorly understood. METHODS: We characterized the lineage and activation status of mononuclear cells in blood and CSF of HIV-infected patients with noncryptococcal meningitis (NCM) (n = 10), those with CM at day 0 (n = 40) or day 14 (n = 21) of antifungal therapy, and those with CM-IRIS (n = 10). RESULTS: At diagnosis, highly activated CD8(+) T cells predominated in CSF in both CM and NCM. CM-IRIS was associated with an increasing frequency of CSF CD4(+) T cells (increased from 2.2% to 23%; P = .06), a shift in monocyte phenotype from classic to an intermediate/proinflammatory, and increased programmed death ligand 1 expression on natural killer cells (increased from 11.9% to 61.6%, P = .03). CSF cellular responses were distinct from responses in peripheral blood. CONCLUSIONS: After CM, T cells in CSF tend to evolve with the development of IRIS, with increasing proportions of activated CD4(+) T cells, migration of intermediate monocytes to the CSF, and declining fungal burden. These changes provide insight into IRIS pathogenesis and could be exploited to more effectively treat CM and prevent CM-IRIS. CI - (c) The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. FAU - Meya, David B AU - Meya DB AD - Infectious Disease Institute School of Medicine, College of Health Sciences Department of Medicine, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis. FAU - Okurut, Samuel AU - Okurut S AD - Makerere University Walter Reed Project, Kampala Uganda. FAU - Zziwa, Godfrey AU - Zziwa G AD - Makerere University Walter Reed Project, Kampala Uganda. FAU - Rolfes, Melissa A AU - Rolfes MA AD - Department of Medicine, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis. FAU - Kelsey, Melander AU - Kelsey M AD - Mucosal and Vaccine Research Program Colorado, University of Colorado Denver, Aurora Denver Veterans Affairs Medical Center. FAU - Cose, Steve AU - Cose S AD - School of Medicine, College of Health Sciences Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS, Entebbe London School of Hygiene and Tropical Medicine, United Kingdom. FAU - Joloba, Moses AU - Joloba M AD - School of Biomedical Sciences, Microbiology Department, Makerere University. FAU - Naluyima, Prossy AU - Naluyima P AD - Makerere University Walter Reed Project, Kampala Uganda. FAU - Palmer, Brent E AU - Palmer BE AD - Mucosal and Vaccine Research Program Colorado, University of Colorado Denver, Aurora. FAU - Kambugu, Andrew AU - Kambugu A AD - Infectious Disease Institute Department of Medicine, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis. FAU - Mayanja-Kizza, Harriet AU - Mayanja-Kizza H AD - School of Medicine, College of Health Sciences. FAU - Bohjanen, Paul R AU - Bohjanen PR AD - Department of Medicine, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis. FAU - Eller, Michael A AU - Eller MA AD - US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring Henry M. Jackson Foundation for the Advancement of Military Medicine. FAU - Wahl, Sharon M AU - Wahl SM AD - National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland. FAU - Boulware, David R AU - Boulware DR AD - Department of Medicine, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis. FAU - Manabe, Yuka C AU - Manabe YC AD - Infectious Disease Institute Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore. FAU - Janoff, Edward N AU - Janoff EN AD - Mucosal and Vaccine Research Program Colorado, University of Colorado Denver, Aurora Denver Veterans Affairs Medical Center. LA - eng GR - R21NS065713/NS/NINDS NIH HHS/United States GR - D43 TW009771/TW/FIC NIH HHS/United States GR - K24AI096925/AI/NIAID NIH HHS/United States GR - K24 AI096925/AI/NIAID NIH HHS/United States GR - NS065713/NS/NINDS NIH HHS/United States GR - R01AI108479/AI/NIAID NIH HHS/United States GR - R01 AI078934/AI/NIAID NIH HHS/United States GR - T32 AI055433/AI/NIAID NIH HHS/United States GR - WT_/Wellcome Trust/United Kingdom GR - R01 AI108479/AI/NIAID NIH HHS/United States GR - 087540/WT_/Wellcome Trust/United Kingdom GR - R01AI078934/AI/NIAID NIH HHS/United States GR - T32AI055433/AI/NIAID NIH HHS/United States GR - U01 AI089244/AI/NIAID NIH HHS/United States GR - R21 NS065713/NS/NINDS NIH HHS/United States GR - U01AI089244/AI/NIAID NIH HHS/United States PT - Journal Article PT - Observational Study PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20141209 PL - United States TA - J Infect Dis JT - The Journal of infectious diseases JID - 0413675 RN - 0 (Anti-Retroviral Agents) SB - IM MH - Adult MH - Anti-Retroviral Agents/adverse effects/*therapeutic use MH - Blood Cells MH - Cerebrospinal Fluid/*cytology MH - Cohort Studies MH - Female MH - HIV Infections/*complications/drug therapy MH - Humans MH - *Immune Reconstitution Inflammatory Syndrome MH - *Lymphocyte Activation MH - Lymphocyte Subsets/immunology MH - Male MH - Meningitis, Cryptococcal/*immunology/*pathology MH - Prospective Studies PMC - PMC4407762 MID - EMS63285 OID - NLM: EMS63285 OTO - NOTNLM OT - HIV OT - cell activation OT - cerebrospinal fluid OT - cryptococcal meningitis OT - cryptococcus OT - immune responses EDAT- 2014/12/11 06:00 MHDA- 2015/06/27 06:00 PMCR- 2014/12/09 CRDT- 2014/12/11 06:00 PHST- 2014/09/24 00:00 [received] PHST- 2014/11/11 00:00 [accepted] PHST- 2014/12/11 06:00 [entrez] PHST- 2014/12/11 06:00 [pubmed] PHST- 2015/06/27 06:00 [medline] PHST- 2014/12/09 00:00 [pmc-release] AID - jiu664 [pii] AID - 10.1093/infdis/jiu664 [doi] PST - ppublish SO - J Infect Dis. 2015 May 15;211(10):1597-606. doi: 10.1093/infdis/jiu664. Epub 2014 Dec 9.