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Antigen-specific interferon-gamma responses and innate cytokine balance in TB-IRIS

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dc.contributor.author Goovaerts, O.
dc.contributor.author Jennes, W.
dc.contributor.author Massinga-Loembe, M.
dc.contributor.author Ceulemans, A.
dc.contributor.author Worodria, W.
dc.contributor.author Mayanja-Kizza, H.
dc.contributor.author Colebunders, R.
dc.contributor.author Kestens, L.
dc.date.accessioned 2015-01-16T16:14:27Z
dc.date.available 2015-01-16T16:14:27Z
dc.date.issued 2014
dc.identifier.issn 1932-6203
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0113101
dc.identifier.other ITG-B1B
dc.identifier.other ITG-B2A
dc.identifier.other ITG-B3B
dc.identifier.other ITG-B4B
dc.identifier.other ITG-C7A
dc.identifier.other ITG-BLA
dc.identifier.other MULTI
dc.identifier.other DBM
dc.identifier.other U-IMMUN
dc.identifier.other DCS
dc.identifier.other U-HIVCLI
dc.identifier.other JIF
dc.identifier.other DOI
dc.identifier.other FTA
dc.identifier.other E-only
dc.identifier.other OAJ
dc.identifier.other Abstract
dc.identifier.other UPD57
dc.identifier.uri http://hdl.handle.net/10390/8212
dc.description.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 IFNgamma 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 IFNgamma 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, TNFalpha and IL-10 by Luminex. Results: Before ART, all responses were similar between TB-IRIS patients and non-IRIS controls. During TB-IRIS, IFNgamma 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 TNFalpha/IL-10 ratios were increased in TB-IRIS patients compared to non-IRIS controls. Conclusion: TB-IRIS patients did not display excessive IFNgamma 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. en_US
dc.language English en_US
dc.subject Viral diseases en_US
dc.subject HIV en_US
dc.subject AIDS en_US
dc.subject Bacterial diseases en_US
dc.subject Tuberculosis en_US
dc.subject Mycobacterium tuberculosis en_US
dc.subject Immune reconstitution inflammatory syndrome (IRIS) en_US
dc.subject IRIS en_US
dc.subject HAART en_US
dc.subject Antiretrovirals en_US
dc.subject Immune response en_US
dc.subject IFN-g en_US
dc.subject Cytokine production en_US
dc.subject ELISPOT en_US
dc.subject IL-6 en_US
dc.subject IL-10 en_US
dc.subject TNF en_US
dc.subject Uganda en_US
dc.subject Africa, East en_US
dc.title Antigen-specific interferon-gamma responses and innate cytokine balance in TB-IRIS en_US
dc.type Article-E en_US
dc.citation.issue 11 en_US
dc.citation.jtitle PLoS ONE en_US
dc.citation.volume 9 en_US
dc.citation.pages e113101 en_US
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/25415590
dc.citation.jabbreviation PLoS ONE en_US


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