Mycobacterial antigen driven activation of CD14++ CD16-monocytes is a predictor of tuberculosis-associated immune reconstitution inflammatory syndrome

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dc.contributor.authorAndrade, Bruno Ben_ZA
dc.contributor.authorSingh, Amriten_ZA
dc.contributor.authorNarendran, Gopalanen_ZA
dc.contributor.authorSchechter, Melissa Een_ZA
dc.contributor.authorNayak, Kaustuven_ZA
dc.contributor.authorSubramanian, Sudhaen_ZA
dc.contributor.authorAnbalagan, Selvarajen_ZA
dc.contributor.authorJensen, Stig M Ren_ZA
dc.contributor.authorPorter, Brian Oen_ZA
dc.contributor.authorAntonelli, Lis Ren_ZA
dc.date.accessioned2015-12-28T06:47:32Z
dc.date.available2015-12-28T06:47:32Z
dc.date.issued2014en_ZA
dc.description.abstractParadoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an aberrant inflammatory response occurring in a subset of TB-HIV co-infected patients initiating anti-retroviral therapy (ART). Here, we examined monocyte activation by prospectively quantitating pro-inflammatory plasma markers and monocyte subsets in TB-HIV co-infected patients from a South Indian cohort at baseline and following ART initiation at the time of IRIS, or at equivalent time points in non-IRIS controls. Pro-inflammatory biomarkers of innate and myeloid cell activation were increased in plasma of IRIS patients pre-ART and at the time of IRIS; this association was confirmed in a second cohort in South Africa. Increased expression of these markers correlated with elevated antigen load as measured by higher sputum culture grade and shorter duration of anti-TB therapy. Phenotypic analysis revealed the frequency of CD14++CD16− monocytes was an independent predictor of TB-IRIS, and was closely associated with plasma levels of CRP, TNF, IL-6 and tissue factor during IRIS. In addition, production of inflammatory cytokines by monocytes was higher in IRIS patients compared to controls pre-ART. These data point to a major role of mycobacterial antigen load and myeloid cell hyperactivation in the pathogenesis of TB-IRIS, and implicate monocytes and monocyte-derived cytokines as potential targets for TB-IRIS prevention or treatment.en_ZA
dc.identifier.apacitationAndrade, B. B., Singh, A., Narendran, G., Schechter, M. E., Nayak, K., Subramanian, S., ... Antonelli, L. R. (2014). Mycobacterial antigen driven activation of CD14++ CD16-monocytes is a predictor of tuberculosis-associated immune reconstitution inflammatory syndrome. <i>PLoS One</i>, http://hdl.handle.net/11427/16032en_ZA
dc.identifier.chicagocitationAndrade, Bruno B, Amrit Singh, Gopalan Narendran, Melissa E Schechter, Kaustuv Nayak, Sudha Subramanian, Selvaraj Anbalagan, Stig M R Jensen, Brian O Porter, and Lis R Antonelli "Mycobacterial antigen driven activation of CD14++ CD16-monocytes is a predictor of tuberculosis-associated immune reconstitution inflammatory syndrome." <i>PLoS One</i> (2014) http://hdl.handle.net/11427/16032en_ZA
dc.identifier.citationAndrade, B. B., Singh, A., Narendran, G., Schechter, M. E., Nayak, K., Subramanian, S., ... & Wilkinson, K. A. (2014). Mycobacterial antigen driven activation of CD14++ CD16-monocytes is a predictor of tuberculosis-associated immune reconstitution inflammatory syndrome. PLoS Pathog, 10(10), e1004433. doi:10.1371/journal.ppat.1004433en_ZA
dc.identifier.ris TY - Journal Article AU - Andrade, Bruno B AU - Singh, Amrit AU - Narendran, Gopalan AU - Schechter, Melissa E AU - Nayak, Kaustuv AU - Subramanian, Sudha AU - Anbalagan, Selvaraj AU - Jensen, Stig M R AU - Porter, Brian O AU - Antonelli, Lis R AB - Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an aberrant inflammatory response occurring in a subset of TB-HIV co-infected patients initiating anti-retroviral therapy (ART). Here, we examined monocyte activation by prospectively quantitating pro-inflammatory plasma markers and monocyte subsets in TB-HIV co-infected patients from a South Indian cohort at baseline and following ART initiation at the time of IRIS, or at equivalent time points in non-IRIS controls. Pro-inflammatory biomarkers of innate and myeloid cell activation were increased in plasma of IRIS patients pre-ART and at the time of IRIS; this association was confirmed in a second cohort in South Africa. Increased expression of these markers correlated with elevated antigen load as measured by higher sputum culture grade and shorter duration of anti-TB therapy. Phenotypic analysis revealed the frequency of CD14++CD16− monocytes was an independent predictor of TB-IRIS, and was closely associated with plasma levels of CRP, TNF, IL-6 and tissue factor during IRIS. In addition, production of inflammatory cytokines by monocytes was higher in IRIS patients compared to controls pre-ART. These data point to a major role of mycobacterial antigen load and myeloid cell hyperactivation in the pathogenesis of TB-IRIS, and implicate monocytes and monocyte-derived cytokines as potential targets for TB-IRIS prevention or treatment. DA - 2014 DB - OpenUCT DO - 10.1371/journal.ppat.1004433 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - Mycobacterial antigen driven activation of CD14++ CD16-monocytes is a predictor of tuberculosis-associated immune reconstitution inflammatory syndrome TI - Mycobacterial antigen driven activation of CD14++ CD16-monocytes is a predictor of tuberculosis-associated immune reconstitution inflammatory syndrome UR - http://hdl.handle.net/11427/16032 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16032
dc.identifier.urihttp://dx.doi.org/10.1371/journal.ppat.1004433
dc.identifier.vancouvercitationAndrade BB, Singh A, Narendran G, Schechter ME, Nayak K, Subramanian S, et al. Mycobacterial antigen driven activation of CD14++ CD16-monocytes is a predictor of tuberculosis-associated immune reconstitution inflammatory syndrome. PLoS One. 2014; http://hdl.handle.net/11427/16032.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThe work is made available under the Creative Commons CC0 public domain dedication.en_ZA
dc.rights.holder© 2014 Andrade et alen_ZA
dc.rights.urihttps://creativecommons.org/publicdomain/en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plospathogensen_ZA
dc.subject.otherMonocytesen_ZA
dc.subject.otherCytokinesen_ZA
dc.subject.otherBiomarkersen_ZA
dc.subject.otherInflammationen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherBlood plasmaen_ZA
dc.subject.otherHIVen_ZA
dc.subject.otherT cellsen_ZA
dc.titleMycobacterial antigen driven activation of CD14++ CD16-monocytes is a predictor of tuberculosis-associated immune reconstitution inflammatory syndromeen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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