Boehringer Ingelheim Animal Health, R&D, Lyon, France.
Université de Lyon, APCSe, Pulmonary and Cardiovascular Agression in Sepsis, VetAgro Sup-Campus Vétérinaire de Lyon, Marcy l'Étoile, France.
Front Immunol. 2020 Oct 9;11:566893. doi: 10.3389/fimmu.2020.566893. eCollection 2020.
Several observations in the world of comparative immunology in plants, insects, fish and eventually mammals lead to the discovery of trained immunity in the early 2010's. The first demonstrations provided evidence that innate immune cells were capable of developing memory after a first encounter with some pathogens. Trained immunity in mammals was initially described in monocytes with the Bacille Calmette-Guerin vaccine (BCG) or prototypical agonists like β-glucans. This phenomenon relies on epigenetic and metabolic modifications leading to an enhanced secretion of inflammatory cytokines when the host encounters homologous or heterologous pathogens. The objective of our research was to investigate the trained immunity, well-described in mouse and human, in other species of veterinary importance. For this purpose, we adapted an model of trained innate immunity in dogs. Blood enriched monocytes were stimulated with β-glucans and we confirmed that it induced an increased production of pro-inflammatory and anti-microbial compounds in response to bacterial stimuli. These results constitute the first demonstration of trained immunity in dogs and confirm its signatures in other mammalian species, with an implication of cellular mechanisms similar to those described in mice and humans regarding cellular epigenetics and metabolic regulations.
在植物、昆虫、鱼类和哺乳动物的比较免疫学领域的几项观察结果，导致了在 21 世纪 10 年代初对训练免疫的发现。最初的证明提供了证据，表明先天免疫细胞在首次接触某些病原体后能够发展出记忆。哺乳动物的训练免疫最初是在单核细胞中描述的，如卡介苗（BCG）或β-葡聚糖等原型激动剂。这种现象依赖于表观遗传和代谢修饰，当宿主遇到同源或异源病原体时，导致炎症细胞因子的分泌增强。我们的研究目的是研究在其他具有兽医重要性的物种中，在小鼠和人类中描述得很好的训练免疫。为此，我们在犬中适应了训练性先天免疫模型。用β-葡聚糖刺激富含单核细胞的血液，我们证实它诱导了对细菌刺激的促炎和抗微生物化合物的增加产生。这些结果首次证明了犬的训练免疫，并证实了其在其他哺乳动物物种中的特征，其细胞机制与在小鼠和人类中描述的关于细胞表观遗传学和代谢调节的机制相似。
