Remot Aude, Carreras Florence, Coupé Anthony, Doz-Deblauwe Émilie, Boschiroli Maria L, Browne John A, Marquant Quentin, Descamps Delphyne, Archer Fabienne, Aseffa Abraham, Germon Pierre, Gordon Stephen V, Winter Nathalie
INRAE, Université de Tours, Nouzilly, France.
Paris-Est University, National Reference Laboratory for Tuberculosis, Animal Health Laboratory, Anses, Maisons-Alfort, France.
Front Vet Sci. 2021 Jul 9;8:696525. doi: 10.3389/fvets.2021.696525. eCollection 2021.
Tuberculosis exacts a terrible toll on human and animal health. While (Mtb) is restricted to humans, (Mb) is present in a large range of mammalian hosts. In cattle, bovine TB (bTB) is a noticeable disease responsible for important economic losses in developed countries and underestimated zoonosis in the developing world. Early interactions that take place between mycobacteria and the lung tissue early after aerosol infection govern the outcome of the disease. In cattle, these early steps remain poorly characterized. The precision-cut lung slice (PCLS) model preserves the structure and cell diversity of the lung. We developed this model in cattle in order to study the early lung response to mycobacterial infection. imaging of PCLS infected with fluorescent Mb revealed bacilli in the alveolar compartment, in adjacent or inside alveolar macrophages, and in close contact with pneumocytes. We analyzed the global transcriptional lung inflammation signature following infection of PCLS with Mb and Mtb in two French beef breeds: Blonde d'Aquitaine and Charolaise. Whereas, lungs from the Blonde d'Aquitaine produced high levels of mediators of neutrophil and monocyte recruitment in response to infection, such signatures were not observed in the Charolaise in our study. In the Blonde d'Aquitaine lung, whereas the inflammatory response was highly induced by two Mb strains, AF2122 isolated from cattle in the UK and Mb3601 circulating in France, the response against two Mtb strains, H37Rv, the reference laboratory strain, and BTB1558, isolated from zebu in Ethiopia, was very low. Strikingly, the type I interferon pathway was only induced by Mb but not Mtb strains, indicating that this pathway may be involved in mycobacterial virulence and host tropism. Hence, the PCLS model in cattle is a valuable tool to deepen our understanding of early interactions between lung host cells and mycobacteria. It revealed striking differences between cattle breeds and mycobacterial strains. This model could help in deciphering biomarkers of resistance vs. susceptibility to bTB in cattle as such information is still critically needed for bovine genetic selection programs and would greatly help the global effort to eradicate bTB.
结核病对人类和动物健康造成了极其严重的损害。虽然结核分枝杆菌（Mtb）仅感染人类，但牛分枝杆菌（Mb）存在于多种哺乳动物宿主中。在牛群中，牛结核病（bTB）是一种显著的疾病，在发达国家造成了重大经济损失，而在发展中世界则是一种被低估的人畜共患病。气溶胶感染后早期分枝杆菌与肺组织之间发生的相互作用决定了疾病的发展结果。在牛群中，这些早期步骤的特征仍不太清楚。精密切割肺片（PCLS）模型保留了肺的结构和细胞多样性。我们在牛身上开发了这个模型，以研究肺部对分枝杆菌感染的早期反应。对感染荧光Mb的PCLS进行成像显示，杆菌存在于肺泡腔、相邻或内部的肺泡巨噬细胞中，并与肺细胞密切接触。我们分析了在两个法国肉牛品种阿基坦黄牛肉牛和夏洛来牛中，用Mb和Mtb感染PCLS后肺部炎症的整体转录特征。然而，在我们的研究中，阿基坦黄牛肉牛的肺部在感染后产生了高水平的中性粒细胞和单核细胞募集介质，而夏洛来牛的肺部未观察到此类特征。在阿基坦黄牛肉牛的肺部，两种Mb菌株，即从英国牛群中分离出的AF2122和在法国传播的Mb3601，强烈诱导了炎症反应，而针对两种Mtb菌株，即参考实验室菌株H37Rv和从埃塞俄比亚瘤牛中分离出的BTB1558的反应则非常低。令人惊讶的是，I型干扰素途径仅由Mb菌株而非Mtb菌株诱导，这表明该途径可能与分枝杆菌的毒力和宿主嗜性有关。因此，牛的PCLS模型是加深我们对肺宿主细胞与分枝杆菌早期相互作用理解的宝贵工具。它揭示了牛品种和分枝杆菌菌株之间的显著差异。该模型有助于破译牛对bTB抗性与易感性的生物标志物，因为此类信息对于牛的遗传选择计划仍然至关重要，并且将极大地推动全球根除bTB的努力。
