Modern lineages of Mycobacterium tuberculosis exhibit lineage-specific patterns of growth and cytokine induction in human monocyte-derived macrophages

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dc.contributor.authorSarkar, Rajeshen_ZA
dc.contributor.authorLenders, Lauraen_ZA
dc.contributor.authorWilkinson, Katalin Aen_ZA
dc.contributor.authorWilkinson, Robert Jen_ZA
dc.contributor.authorNicol, Mark Pen_ZA
dc.date.accessioned2016-01-02T05:07:45Z
dc.date.available2016-01-02T05:07:45Z
dc.date.issued2012en_ZA
dc.description.abstractBACKGROUND: Strains of Mycobacterium tuberculosis vary in virulence. Strains that have caused outbreaks in the United States and United Kingdom have been shown to subvert the innate immune response as a potential immune evasion mechanism. There is, however, little information available as to whether these patterns of immune subversion are features of individual strains or characteristic of broad clonal lineages of M. tuberculosis . METHODS: Strains from two major modern lineages (lineage 2 [East-Asian] and lineage 4 [Euro-American]) circulating in the Western Cape in South Africa as well as a comparator modern lineage (lineage 3 [CAS/Delhi]) were identified. We assessed two virulence associated characteristics: mycobacterial growth (in liquid broth and monocyte derived macrophages) and early pro-inflammatory cytokine induction. RESULTS: In liquid culture, Lineage 4 strains grew more rapidly and reached higher plateau levels than other strains (lineage 4 vs. lineage 2 p = 0.0024; lineage 4 vs. lineage 3 p = 0.0005). Lineage 3 strains were characterized by low and early plateau levels, while lineage 2 strains showed an intermediate growth phenotype. In monocyte-derived macrophages, lineage 2 strains grew faster than lineage 3 strains (p<0.01) with lineage 4 strains having an intermediate phenotype. Lineage 2 strains induced the lowest levels of pro-inflammatory TNF and IL-12p40 as compared to other lineages (lineage 2: median TNF 362 pg/ml, IL-12p40 91 pg/ml; lineage 3: median TNF 1818 pg/ml, IL-12p40 123 pg/ml; lineage 4: median TNF 1207 pg/ml, IL-12p40 205 pg/ml;). In contrast, lineage 4 strains induced high levels of IL-12p40 and intermediate level of TNF. Lineage 3 strains induced high levels of TNF and intermediate levels of IL-12p40. CONCLUSIONS: Strains of M. tuberculosis from the three major modern strain lineages possess distinct patterns of growth and cytokine induction. Rapid growth and immune subversion may be key characteristics to the success of these strains in different human populations.en_ZA
dc.identifier.apacitationSarkar, R., Lenders, L., Wilkinson, K. A., Wilkinson, R. J., & Nicol, M. P. (2012). Modern lineages of Mycobacterium tuberculosis exhibit lineage-specific patterns of growth and cytokine induction in human monocyte-derived macrophages. <i>PLoS One</i>, http://hdl.handle.net/11427/16180en_ZA
dc.identifier.chicagocitationSarkar, Rajesh, Laura Lenders, Katalin A Wilkinson, Robert J Wilkinson, and Mark P Nicol "Modern lineages of Mycobacterium tuberculosis exhibit lineage-specific patterns of growth and cytokine induction in human monocyte-derived macrophages." <i>PLoS One</i> (2012) http://hdl.handle.net/11427/16180en_ZA
dc.identifier.citationSarkar, R., Lenders, L., Wilkinson, K. A., Wilkinson, R. J., & Nicol, M. P. (2011). Modern lineages of Mycobacterium tuberculosis exhibit lineage-specific patterns of growth and cytokine induction in human monocyte-derived macrophages. PloS one, 7(8), e43170. doi:10.1371/journal.pone.0043170en_ZA
dc.identifier.ris TY - Journal Article AU - Sarkar, Rajesh AU - Lenders, Laura AU - Wilkinson, Katalin A AU - Wilkinson, Robert J AU - Nicol, Mark P AB - BACKGROUND: Strains of Mycobacterium tuberculosis vary in virulence. Strains that have caused outbreaks in the United States and United Kingdom have been shown to subvert the innate immune response as a potential immune evasion mechanism. There is, however, little information available as to whether these patterns of immune subversion are features of individual strains or characteristic of broad clonal lineages of M. tuberculosis . METHODS: Strains from two major modern lineages (lineage 2 [East-Asian] and lineage 4 [Euro-American]) circulating in the Western Cape in South Africa as well as a comparator modern lineage (lineage 3 [CAS/Delhi]) were identified. We assessed two virulence associated characteristics: mycobacterial growth (in liquid broth and monocyte derived macrophages) and early pro-inflammatory cytokine induction. RESULTS: In liquid culture, Lineage 4 strains grew more rapidly and reached higher plateau levels than other strains (lineage 4 vs. lineage 2 p = 0.0024; lineage 4 vs. lineage 3 p = 0.0005). Lineage 3 strains were characterized by low and early plateau levels, while lineage 2 strains showed an intermediate growth phenotype. In monocyte-derived macrophages, lineage 2 strains grew faster than lineage 3 strains (p<0.01) with lineage 4 strains having an intermediate phenotype. Lineage 2 strains induced the lowest levels of pro-inflammatory TNF and IL-12p40 as compared to other lineages (lineage 2: median TNF 362 pg/ml, IL-12p40 91 pg/ml; lineage 3: median TNF 1818 pg/ml, IL-12p40 123 pg/ml; lineage 4: median TNF 1207 pg/ml, IL-12p40 205 pg/ml;). In contrast, lineage 4 strains induced high levels of IL-12p40 and intermediate level of TNF. Lineage 3 strains induced high levels of TNF and intermediate levels of IL-12p40. CONCLUSIONS: Strains of M. tuberculosis from the three major modern strain lineages possess distinct patterns of growth and cytokine induction. Rapid growth and immune subversion may be key characteristics to the success of these strains in different human populations. DA - 2012 DB - OpenUCT DO - 10.1371/journal.pone.0043170 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - Modern lineages of Mycobacterium tuberculosis exhibit lineage-specific patterns of growth and cytokine induction in human monocyte-derived macrophages TI - Modern lineages of Mycobacterium tuberculosis exhibit lineage-specific patterns of growth and cytokine induction in human monocyte-derived macrophages UR - http://hdl.handle.net/11427/16180 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16180
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0043170
dc.identifier.vancouvercitationSarkar R, Lenders L, Wilkinson KA, Wilkinson RJ, Nicol MP. Modern lineages of Mycobacterium tuberculosis exhibit lineage-specific patterns of growth and cytokine induction in human monocyte-derived macrophages. PLoS One. 2012; http://hdl.handle.net/11427/16180.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Medical Biochemistryen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© Sarkar et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherCytokinesen_ZA
dc.subject.otherMacrophagesen_ZA
dc.subject.otherMonocytesen_ZA
dc.subject.otherAlveolar macrophagesen_ZA
dc.subject.otherSouth Africaen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherCell culturesen_ZA
dc.titleModern lineages of Mycobacterium tuberculosis exhibit lineage-specific patterns of growth and cytokine induction in human monocyte-derived macrophagesen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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