Variation in the Early Host-Pathogen Interaction of Bovine Macrophages with Divergent Mycobacterium bovis Strains in the United Kingdom

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dc.contributor.authorJensen, Kirsty
dc.contributor.authorGallagher, Iain J.
dc.contributor.authorJohnston, Nicholas
dc.contributor.authorWelsh, Michael
dc.contributor.authorSkuce, Robin A.
dc.contributor.authorWilliams, John L.
dc.contributor.authorGlass, Elizabeth J. Glass
dc.date.accessioned2021-06-11T15:30:46Z
dc.date.available2021-06-11T15:30:46Z
dc.date.issued2018-02-20
dc.descriptionPublication history: Accepted - 8 December 2017; Published online - 20 December 2017.en_US
dc.description.abstractBovine tuberculosis has been an escalating animal health issue in the United Kingdom since the 1980s, even though control policies have been in place for over 60 years. The importance of the genetics of the etiological agent, Mycobacterium bovis, in the reemergence of the disease has been largely overlooked. We compared the interaction between bovine monocyte-derived macrophages (bMDM) and two M. bovis strains, AF2122/97 and G18, representing distinct genotypes currently circulating in the United Kingdom. These M. bovis strains exhibited differences in survival and growth in bMDM. Although uptake was similar, the number of viable intracellular AF2122/97 organisms increased rapidly, while G18 growth was constrained for the first 24 h. AF2122/97 infection induced a greater transcriptional response by bMDM than G18 infection with respect to the number of differentially expressed genes and the fold changes measured. AF2122/97 infection induced more bMDM cell death, with characteristics of necrosis and apoptosis, more inflammasome activation, and a greater type I interferon response than G18. In conclusion, the two investigated M. bovis strains interact in significantly different ways with the host macrophage. In contrast to the relatively silent infection by G18, AF2122/97 induces greater signaling to attract other immune cells and induces host cell death, which may promote secondary infections of naive macrophages. These differences may affect early events in the host-pathogen interaction, including granuloma development, which could in turn alter the progression of the disease. Therefore, the potential involvement of M. bovis genotypes in the reemergence of bovine tuberculosis in the United Kingdom warrants further investigation.en_US
dc.description.sponsorshipRecombinant TNF and IL-10 were provided under the auspices of the Biotechnology and Biological Sciences Research Council (BBSRC) grants (BB/I019863/1 and BB/I020519/1) with the support of the Scottish Government as an Industrial Partnership Award with AbD Serotec (a Bio-Rad Company). This work was supported by the European Framework 7 small collaborative project MACROSYS (FP7-KBBE-2007-1-1-2). E.J.G. was also supported by a BBSRC Strategic Programme grant (Control of Infectious Diseases [BB/P013740/1])en_US
dc.identifierhttp://hdl.handle.net/20.500.12518/280
dc.identifier.citationJensen, K., Gallagher, I. J., Johnston, N., Welsh, M., Skuce, R., Williams, J. L. and Glass, E. J. (2018) ‘Variation in the Early Host-Pathogen Interaction of Bovine Macrophages with Divergent Mycobacterium bovis Strains in the United Kingdom’, Infection and Immunity. Edited by S. Ehrt, 86(3). doi: 10.1128/iai.00385-17.en_US
dc.identifier.issn0019-9567
dc.identifier.urihttps://doi.org/10.1128/IAI.00385-17
dc.language.isoenen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.rights© 2018 Jensen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International licenseen_US
dc.subjectMycobacteriumen_US
dc.subjectcattleen_US
dc.subjecthost-pathogen interactionsen_US
dc.subjectmacrophagesen_US
dc.titleVariation in the Early Host-Pathogen Interaction of Bovine Macrophages with Divergent Mycobacterium bovis Strains in the United Kingdomen_US
dc.typeArticleen_US
dcterms.dateAccepted2017-12-08
dcterms.dateSubmitted2017-05-26

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