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

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Original languageEnglish
Article numbere00385-17
JournalInfection and Immunity
Volume86
Issue number3
Early online date20 Dec 2017
DOIs
Publication statusPublished - Mar 2018

Abstract

Bovine 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 twoM. bovisstrains, AF2122/97 and G18, representing distinct genotypes currently circulating in the United Kingdom. TheseM. bovisstrains 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 investigatedM. bovisstrains 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 ofM. bovisgenotypes in the reemergence of bovine tuberculosis in the United Kingdom warrants further investigation.

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