Compartmentalization of innate immune responses in the central nervous system during cryptococcal meningitis/HIV coinfection

Vivek Naranbhai, Christina Catherine Chang, Raveshni Durgiah, Saleha Omarjee, Andrew Lim, Mahomed-Yunus Suleman Moosa, Julian Elliott, Thumbi Ndung'u, Sharon Ruth Lewin, Martyn A French, William H Carr

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17 Citations (Scopus)


Abstract Objective: The role of innate immunity in the pathogenesis of cryptococcal meningitis is unclear. We hypothesized that natural killer (NK) cell and monocyte responses show central nervous system (CNS) compartment-specific profiles, and are altered by antifungal therapy and combination antiretroviral therapy (cART) during cryptococcal meningitis/HIV coinfection. Design: Substudy of a prospective cohort study of adults with cryptococcal meningitis/HIV coinfection in Durban, South Africa. Methods: We used multiparametric flow cytometry to study compartmentalization of subsets, CD69 (a marker of activation), CXCR3 and CX3CR1 expression, and cytokine secretion of NK cells and monocytes in freshly collected blood and cerebrospinal fluid (CSF) at diagnosis (n=23), completion of antifungal therapy induction (n=19), and after a further 4 weeks of cART (n=9). Results: Relative to blood, CSF was enriched with CD56bright (immunoregulatory) NK cells (P=0.0004). At enrolment, CXCR3 expression was more frequent among blood CD56bright than either blood CD56dim (P
Original languageEnglish
Pages (from-to)657 - 666
Number of pages10
Issue number5
Publication statusPublished - 2014

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