The host response to a clinical MDR mycobacterial strain cultured in a detergent-free environment : a global transcriptomics approach

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dc.contributor.authorLeisching, Ginaen_ZA
dc.contributor.authorPietersen, Ray-Deanen_ZA
dc.contributor.authorMpongoshe, Vuyisekaen_ZA
dc.contributor.authorVan Heerden, Carelen_ZA
dc.contributor.authorVan Helden, Paulen_ZA
dc.contributor.authorWiid, Ianen_ZA
dc.contributor.authorBaker, Bienyameenen_ZA
dc.date.accessioned2017-10-09T12:14:07Z
dc.date.available2017-10-09T12:14:07Z
dc.date.issued2016
dc.descriptionCITATION: Leisching, G., et al. 2016. The host response to a clinical MDR mycobacterial strain cultured in a detergent-free environment : a global transcriptomics approach. PLoS ONE, 11(4):e0153079, doi:10.1371/journal.pone.0153079.en_ZA
dc.descriptionThe original publication is available at http://journals.plos.org/plosoneen_ZA
dc.description.abstractDuring Mycobacterium tuberculosis (M.tb) infection, the initial interactions between the pathogen and the host cell determines internalization and innate immune response events. It is established that detergents such as Tween alter the mycobacterial cell wall and solubilize various lipids and proteins. The implication of this is significant since induced changes on the cell wall affect macrophage uptake and the immune response to M.tb. Importantly, during transmission between hosts, aerosolized M.tb enters the host in its native form, i.e. in a detergent-free environment, thus in vitro and in vivo studies should mimic this as closely as possible. To this end, we have optimized a procedure for growing and processing detergent-free M.tb and assessed the response of murine macrophages (BMDM) infected with multi drug-resistant M.tb (R179 Beijing 220 clinical isolate) using RNAseq. We compared the effects of the host response to M.tb cultured under standard laboratory conditions (Tween 80 containing medium -R179T), or in detergent-free medium (R179NT). RNAseq comparisons reveal 2651 differentially expressed genes in BMDMs infected with R179T M.tb vs. BMDMs infected with R179NT M.tb. A range of differentially expressed genes involved in BMDM receptor interaction with M.tb (Mrc1, Ifngr1, Tlr9, Fpr1 and Itgax) and pro-inflammatory cytokines/chemokines (Il6, Il1b, Tnf, Ccl5 and Cxcl14) were selected for analysis through qPCR. BMDMs infected with R179NT stimulate a robust inflammatory response. Interestingly, R179NT M.tb induce transcription of Fpr1, a receptor which detects bacterial formyl peptides and initiates a myriad of immune responses. Additionally we show that the host components Cxcl14, with an unknown role in M.tb infection, and Tlr9, an emerging role player, are only stimulated by infection with R179NT M.tb. Taken together, our results suggest that the host response differs significantly in response to Tween 80 cultured M.tb and should therefore not be used in infection experiments.en_ZA
dc.description.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0153079en_ZA
dc.description.versionPublisher's versionen_ZA
dc.format.extent16 pages : illustrations (chiefly colour)en_ZA
dc.identifier.citationLeisching, G., et al. 2016. The host response to a clinical MDR mycobacterial strain cultured in a detergent-free environment : a global transcriptomics approach. PLoS ONE, 11(4):e0153079, doi:10.1371/journal.pone.0153079en_ZA
dc.identifier.issn1932-6203 (online)
dc.identifier.otherdoi:10.1371/journal.pone.0153079
dc.identifier.urihttp://hdl.handle.net/10019.1/102300en_ZA
dc.language.isoen_ZAen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectMycobacterium tuberculosisen_ZA
dc.subjectMycobacterial strainsen_ZA
dc.subjectDetergent free environmenten_ZA
dc.subjectCultured strainsen_ZA
dc.titleThe host response to a clinical MDR mycobacterial strain cultured in a detergent-free environment : a global transcriptomics approachen_ZA
dc.typeArticleen_ZA
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