Division of Infection & Immunity, The Roslin Institute & R(D)SVS, University of Edinburgh, Easter Bush Campus, Midlothian, United Kingdom
Division of Infection & Immunity, The Roslin Institute & R(D)SVS, University of Edinburgh, Easter Bush Campus, Midlothian, United Kingdom.
Infect Immun. 2018 Feb 20;86(3). doi: 10.1128/IAI.00385-17. Print 2018 Mar.
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, , in the reemergence of the disease has been largely overlooked. We compared the interaction between bovine monocyte-derived macrophages (bMDM) and two strains, AF2122/97 and G18, representing distinct genotypes currently circulating in the United Kingdom. These 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 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 genotypes in the reemergence of bovine tuberculosis in the United Kingdom warrants further investigation.
自 20 世纪 80 年代以来，牛结核病一直是英国不断升级的动物健康问题，尽管控制政策已经实施了 60 多年。在疾病再次出现的过程中，病原 的遗传学的重要性在很大程度上被忽视了。我们比较了两种 菌株，AF2122/97 和 G18，在牛单核细胞衍生的巨噬细胞（bMDM）中的相互作用，它们代表了目前在英国循环的两种不同基因型。这些 菌株在 bMDM 中的存活和生长表现出差异。尽管摄取量相似，但活体内 AF2122/97 生物的数量迅速增加，而 G18 的生长在前 24 小时受到限制。与 G18 感染相比，AF2122/97 感染诱导 bMDM 的转录反应更大，表现在差异表达基因的数量和测量的倍数变化方面。与 G18 相比，AF2122/97 感染诱导更多的 bMDM 细胞死亡，具有坏死和凋亡的特征，更多的炎症小体激活和更强的 I 型干扰素反应。总之，两种研究的 菌株与宿主巨噬细胞以显著不同的方式相互作用。与 G18 相对沉默的感染相反，AF2122/97 诱导更大的信号以吸引其他免疫细胞，并诱导宿主细胞死亡，这可能促进幼稚巨噬细胞的继发感染。这些差异可能影响宿主-病原体相互作用的早期事件，包括肉芽肿的发展，这反过来又可能改变疾病的进展。因此， 基因型在英国牛结核病再次出现中的潜在参与值得进一步研究。
