期刊
JOURNAL OF INFECTIOUS DISEASES
卷 211, 期 10, 页码 1597-1606出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiu664
关键词
cryptococcal meningitis; cryptococcus; HIV; cerebrospinal fluid; immune responses; cell activation
资金
- National Institutes of Health [R01AI078934, U01AI089244, NS065713, R01AI108479, K24AI096925, T32AI055433, R21NS065713]
- Wellcome Trust (Training Health Researchers into Vocational Excellence [THRiVE]) in East Africa [087540]
- GlaxoSmithKline Collaborative Investigator Research Award
- Veterans Affairs Research Service
Methods.aEuro integral 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.aEuro integral 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.aEuro integral 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.
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