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dc.contributor.authorTonby, Kristian
dc.contributor.authorWergeland, Ida
dc.contributor.authorLieske, Nora V
dc.contributor.authorKvale, Dag
dc.contributor.authorTasken, Kjetil
dc.contributor.authorDyrhol-Riise, Anne M
dc.date.accessioned2016-10-25T03:36:59Z
dc.date.available2016-10-25T03:36:59Z
dc.date.issued2016
dc.identifier.citationBMC Infectious Diseases. 2016 Oct 24;16(1):599
dc.identifier.urihttp://hdl.handle.net/10852/52936
dc.description.abstractBackground Tuberculosis (TB) causes a major burden on global health with long and cumbersome TB treatment regimens. Host-directed immune modulating therapies have been suggested as adjunctive treatment to TB antibiotics. Upregulated cyclooxygenase-2 (COX-2)-prostaglandin E2 (PGE2) signaling pathway may cause a dysfunctional immune response that favors survival and replication of Mycobacterium tuberculosis (Mtb). Methods Blood samples were obtained from patients with latent TB (n = 9) and active TB (n = 33) before initiation of anti-TB chemotherapy. COX-2 expression in monocytes and ESAT-6 and Ag85 specific T cell cytokine responses (TNF-α, IFN-γ, IL-2), proliferation (carboxyfluorescein succinimidyl ester staining) and regulation (FOXP3+ T regulatory cells) were analysed by flow cytometry and the in vitro effects of the COX-1/2 inhibitor indomethacin were measured. Results We demonstrate that indomethacin significantly down-regulates the fraction of Mtb specific FOXP3+ T regulatory cells (ESAT-6; p = 0.004 and Ag85; p < 0.001) with a concomitant reduction of Mtb specific cytokine responses and T cell proliferation in active TB. Although active TB tend to have higher levels, there are no significant differences in COX-2 expression between unstimulated monocytes from patients with active TB compared to latent infection. Monocytes in both TB groups respond with a significant upregulation of COX-2 after in vitro stimulation. Conclusions Taken together, our in vitro data indicate a modulation of the Th1 effector and T regulatory cells in Mtb infection in response to the COX-1/2 inhibitor indomethacin. The potential role as adjunctive host-directed therapy in TB disease should be further evaluated in both animal studies and in human clinical trials.
dc.language.isoeng
dc.rightsThe Author(s).
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleThe COX- inhibitor indomethacin reduces Th1 effector and T regulatory cells in vitro in Mycobacterium tuberculosis infection
dc.typeJournal article
dc.date.updated2016-10-25T03:37:00Z
dc.creator.authorTonby, Kristian
dc.creator.authorWergeland, Ida
dc.creator.authorLieske, Nora V
dc.creator.authorKvale, Dag
dc.creator.authorTasken, Kjetil
dc.creator.authorDyrhol-Riise, Anne M
dc.identifier.doihttp://dx.doi.org/10.1186/s12879-016-1938-8
dc.identifier.urnURN:NBN:no-56277
dc.type.documentTidsskriftartikkel
dc.type.peerreviewedPeer reviewed
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/52936/1/12879_2016_Article_1938.pdf
dc.type.versionPublishedVersion
cristin.articleid599


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