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J Infect Dis. 2015 May 15;211(10):1597-606. doi: 10.1093/infdis/jiu664. Epub 2014 Dec 9.

Cellular immune activation in cerebrospinal fluid from ugandans with cryptococcal meningitis and immune reconstitution inflammatory syndrome.

Author information

1
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.
2
Makerere University Walter Reed Project, Kampala Uganda.
3
Department of Medicine, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis.
4
Mucosal and Vaccine Research Program Colorado, University of Colorado Denver, Aurora Denver Veterans Affairs Medical Center.
5
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.
6
School of Biomedical Sciences, Microbiology Department, Makerere University.
7
Mucosal and Vaccine Research Program Colorado, University of Colorado Denver, Aurora.
8
Infectious Disease Institute Department of Medicine, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis.
9
School of Medicine, College of Health Sciences.
10
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring Henry M. Jackson Foundation for the Advancement of Military Medicine.
11
National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland.
12
Infectious Disease Institute Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore.

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.

KEYWORDS:

HIV; cell activation; cerebrospinal fluid; cryptococcal meningitis; cryptococcus; immune responses

PMID:
25492918
PMCID:
PMC4407762
DOI:
10.1093/infdis/jiu664
[Indexed for MEDLINE]
Free PMC Article

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