Title
Antigen-specific interferon-gamma responses and innate cytokine balance in TB-IRIS Antigen-specific interferon-gamma responses and innate cytokine balance in TB-IRIS
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Faculty of Medicine and Health Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
Subject
Engineering sciences. Technology
Source (journal)
PLoS ONE
Volume/pages
9(2014) :11 , 16 p.
ISSN
1932-6203
1932-6203
Article Reference
e113101
Carrier
E-only publicatie
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB patients receiving antiretroviral therapy (ART). TB-IRIS could be associated with an exaggerated immune response to TB-antigens. We compared the recovery of IFN gamma responses to recall and TB-antigens and explored in vitro innate cytokine production in TB-IRIS patients. Methods: In a prospective cohort study of HIV-TB co-infected patients treated for TB before ART initiation, we compared 18 patients who developed TB-IRIS with 18 non-IRIS controls matched for age, sex and CD4 count. We analyzed IFN gamma ELISpot responses to CMV, influenza, TB and LPS before ART and during TB-IRIS. CMV and LPS stimulated ELISpot supernatants were subsequently evaluated for production of IL-12p70, IL-6, TNF alpha and IL-10 by Luminex. Results: Before ART, all responses were similar between TB-IRIS patients and non-IRIS controls. During TB-IRIS, IFN gamma responses to TB and influenza antigens were comparable between TB-IRIS patients and non-IRIS controls, but responses to CMV and LPS remained significantly lower in TB-IRIS patients. Production of innate cytokines was similar between TB-IRIS patients and non-IRIS controls. However, upon LPS stimulation, IL-6/IL-10 and TNF alpha/IL-10 ratios were increased in TB-IRIS patients compared to non-IRIS controls. Conclusion: TB-IRIS patients did not display excessive IFN gamma responses to TB-antigens. In contrast, the reconstitution of CMV and LPS responses was delayed in the TB-IRIS group. For LPS, this was linked with a pro-inflammatory shift in the innate cytokine balance. These data are in support of a prominent role of the innate immune system in TB-IRIS.
Full text (open access)
https://repository.uantwerpen.be/docman/irua/c0e8ba/9434.pdf
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