title: Cellular immune activation in cerebrospinal fluid from ugandans with cryptococcal meningitis and immune reconstitution inflammatory syndrome.
abstract: 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.
authors.affiliation: 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.
authors.forename: David B
authors.initials: DB
authors.lastname: Meya
authors.affiliation: Makerere University Walter Reed Project, Kampala Uganda.
authors.forename: Samuel
authors.initials: S
authors.lastname: Okurut
authors.affiliation: Makerere University Walter Reed Project, Kampala Uganda.
authors.forename: Godfrey
authors.initials: G
authors.lastname: Zziwa
authors.affiliation: Department of Medicine, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Rolfes
authors.affiliation: Mucosal and Vaccine Research Program Colorado, University of Colorado Denver, Aurora Denver Veterans Affairs Medical Center.
authors.forename: Melander
authors.initials: M
authors.lastname: Kelsey
authors.affiliation: 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.
authors.forename: Steve
authors.initials: S
authors.lastname: Cose
authors.affiliation: School of Biomedical Sciences, Microbiology Department, Makerere University.
authors.forename: Moses
authors.initials: M
authors.lastname: Joloba
authors.affiliation: Makerere University Walter Reed Project, Kampala Uganda.
authors.forename: Prossy
authors.initials: P
authors.lastname: Naluyima
authors.affiliation: Mucosal and Vaccine Research Program Colorado, University of Colorado Denver, Aurora.
authors.forename: Brent E
authors.initials: BE
authors.lastname: Palmer
authors.affiliation: Infectious Disease Institute Department of Medicine, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kambugu
authors.affiliation: School of Medicine, College of Health Sciences.
authors.forename: Harriet
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.affiliation: Department of Medicine, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Bohjanen
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring Henry M. Jackson Foundation for the Advancement of Military Medicine.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Eller
authors.affiliation: National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Wahl
authors.affiliation: Department of Medicine, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis.
authors.forename: David R
authors.initials: DR
authors.lastname: Boulware
authors.affiliation: Infectious Disease Institute Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore.
authors.forename: Yuka C
authors.initials: YC
authors.lastname: Manabe
authors.affiliation: Mucosal and Vaccine Research Program Colorado, University of Colorado Denver, Aurora Denver Veterans Affairs Medical Center.
authors.forename: Edward N
authors.initials: EN
authors.lastname: Janoff
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001773:Blood Cells; D002555:Cerebrospinal Fluid / Q000166:cytology*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D016919:Meningitis, Cryptococcal / Q000276:immunology* / Q000473:pathology*; D011446:Prospective Studies
chemical_list: D044966:Anti-Retroviral Agents
keywords: HIV; cell activation; cerebrospinal fluid; cryptococcal meningitis; cryptococcus; immune responses