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dc.contributor.authorKeane, Joseph
dc.date.accessioned2019-09-13T09:25:37Z
dc.date.available2019-09-13T09:25:37Z
dc.date.issued2012
dc.date.submitted2012en
dc.identifier.citationMacdonald SH-F, Woodward E, Coleman MM, Dorris ER, Nadarajan P, et al. (2012) Networked T Cell Death following Macrophage Infection byMycobacterium tuberculosis. PLoS ONE 7(6): e38488en
dc.identifier.issn1932-6203
dc.identifier.otherY
dc.identifier.urihttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0038488
dc.identifier.urihttp://hdl.handle.net/2262/89489
dc.descriptionPUBLISHEDen
dc.description.abstractBackground: Depletion of T cells following infection by Mycobacterium tuberculosis (Mtb) impairs disease resolution, and interferes with clinical test performance that relies on cell-mediated immunity. A number of mechanisms contribute to this T cell suppression, such as activation-induced death and trafficking of T cells out of the peripheral circulation and into the diseased lungs. The extent to which Mtb infection of human macrophages affects T cell viability however, is not well characterised. Methodology/Principal Findings: We found that lymphopenia (<1.5×109 cells/l) was prevalent among culture-positive tuberculosis patients, and lymphocyte counts significantly improved post-therapy. We previously reported that Mtb-infected human macrophages resulted in death of infected and uninfected bystander macrophages. In the current study, we sought to examine the influence of infected human alveolar macrophages on T cells. We infected primary human alveolar macrophages (the primary host cell for Mtb) or PMA-differentiated THP-1 cells with Mtb H37Ra, then prepared cell-free supernatants. The supernatants of Mtb-infected macrophages caused dose-dependent, caspase-dependent, T cell apoptosis. This toxic effect of infected macrophage secreted factors did not require TNF-α or Fas. The supernatant cytotoxic signal(s) were heat-labile and greater than 50 kDa in molecular size. Although ESAT-6 was toxic to T cells, other Mtb-secreted factors tested did not influence T cell viability; nor did macrophage-free Mtb bacilli or broth from Mtb cultures. Furthermore, supernatants from Mycobacterium bovis Bacille de Calmette et Guerin (BCG)- infected macrophages also elicited T cell death suggesting that ESAT-6 itself, although cytotoxic, was not the principal mediator of T cell death in our system. Conclusions: Mtb-Infected macrophages secrete heat-labile factors that are toxic to T cells, and may contribute to the immunosuppression seen in tuberculosis as well as interfere with microbial eradication in the granuloma.en
dc.format.extente38488en
dc.language.isoenen
dc.relation.ispartofseriesPloS one;
dc.relation.ispartofseries7;
dc.relation.ispartofseries6;
dc.rightsYen
dc.subjectMycobacterium tuberculosis (Mtb)en
dc.subjectLymphopeniaen
dc.subjectHuman alveolar macrophagesen
dc.subjectT cellsen
dc.titleNetworked T Cell Death following Macrophage Infection by Mycobacterium tuberculosis.en
dc.typeJournal Articleen
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/josephmk
dc.identifier.rssinternalid79807
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0038488
dc.rights.ecaccessrightsopenAccess
dc.contributor.sponsorGrantNumber7/SRC/B1144en
dc.identifier.orcid_id0000-0001-5313-385X


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