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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Compartmentalization of innate immune responses in the central nervous system during cryptococcal meningitis/HIV coinfection
AIDS, Volume 28, No. 5, Year 2014
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Description
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<0.0001) or CSF CD56bright (P=0.0002) NK cells. Antifungal therapy diminished blood (P<0.05), but not CSF CXCR3pos NK-cell proportions nor CX3CR1pos NK-cell proportions. CD56 bright and CD56dim NK cells were more activated in CSF than blood (P<0.0001). Antifungal therapy induction reduced CD56 dim NK-cell activation in CSF (P=0.02). Activation of blood CD56 bright and CD56dim NK cells was diminished following cART commencement (P<0.0001, P=0.03). Immunoregulatory NK cells in CSF tended to secrete higher levels of CXCL10 (P=0.06) and lower levels of tumor necrosis factor α (P=0.06) than blood immunoregulatory NK cells. CSF was enriched with nonclassical monocytes (P=0.001), but antifungal therapy restored proportions of classical monocytes (P=0.007). Conclusion: These results highlight CNS activation, trafficking, and function of NK cells and monocytes in cryptococcal meningitis/HIV and implicate immunoregulatory NK cells and proinflammatory monocytes as potential modulators of cryptococcal meningitis pathogenesis during HIV coinfection. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Authors & Co-Authors
Naranbhai, Vivek
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
South Africa, Durban
The Nelson R. Mandela Medical School
United Kingdom, Oxford
Nuffield Department of Medicine
Chang, Christina C.
South Africa, Durban
The Nelson R. Mandela Medical School
Australia, Clayton
Monash University
Australia, Melbourne
Burnet Institute
Durgiah, Raveshni
South Africa, Durban
The Nelson R. Mandela Medical School
Omarjee, Saleha
South Africa, Durban
The Nelson R. Mandela Medical School
Lim, Andrew
Australia, Perth
The University of Western Australia
Moosa, Mohamed Yunus Suleman
South Africa, Durban
The Nelson R. Mandela Medical School
Elliott, Julian H.
Australia, Clayton
Monash University
Australia, Melbourne
Burnet Institute
Ndung'u, Thumbi P.
South Africa, Durban
The Nelson R. Mandela Medical School
South Africa, Durban
University of Kwazulu-natal
Germany, Berlin
Max Planck Institute for Infection Biology
Lewin, Sharon R.
Australia, Clayton
Monash University
Australia, Melbourne
Burnet Institute
French, Martyn A.H.
Australia, Perth
The University of Western Australia
Carr, William Henry
South Africa, Durban
The Nelson R. Mandela Medical School
United States, New York
The City University of new York
Statistics
Citations: 18
Authors: 11
Affiliations: 9
Identifiers
Doi:
10.1097/QAD.0000000000000200
e-ISSN:
14735571
Research Areas
Cancer
Infectious Diseases
Study Design
Cohort Study
Study Approach
Quantitative
Study Locations
South Africa