Filor Viviane, Myslinska Joanna, Saliani Amitis, Dalli Jesmond, Olinga Peter, Bäumer Wolfgang, Werling Dirk
School of Veterinary Medicine, Institute of Pharmacology and Toxicology, Freie Universität Berlin, Berlin, Germany.
Centre for Vaccinology and Regenerative Medicine, Department of Pathobiology and Population Sciences, Royal Veterinary College, North Mymms, UK.
Innate Immun. 2025 Jan-Dec;31:17534259251360484. doi: 10.1177/17534259251360484. Epub 2025 Aug 21.
Mastitis in cattle poses a significant health challenge and results in substantial economic losses for the dairy industry. This study aimed to extend the existing precision-cut bovine udder slices (PCBUS) model as an model to explore the potential of inducing trained immunity in the udder with the goal to use the resulting knowledge for potential new treatment strategies. Interestingly, incubation of PCBUS with 10% fetal calf serum (FCS), but no 2% or FCS-free, negatively affected the production of some of the chemokines/cytokines analysed. When trained immunity was induced by zymosan, followed by stimulation with -derived lipopolysaccharide (LPS), production of interleukin (IL)-1β, IL-6, tumor necrosis factor α and interferon (IFNγ) was downregulated while production of IL-17A and pro-resolving lipid mediators (leukotrienes and prostaglandins) was upregulated. While the current experimental setup did not definitively confirm the induction of trained immunity for all parameters analysed in PCBUS, it validated the utility of PCBUS as a robust model for studying bovine udder inflammation. This model offers a promising platform for developing innovative mastitis treatments, particularly given the growing concern over antimicrobial resistance, as well as offering alternatives to the use of live animals in experimental studies in line with the 3Rs principles. It also provides a valuable tool for advancing our understanding of immune responses in the bovine udder. By adapting the precision-cut tissue slice technique to bovine udders, this model enables extensive research into new therapeutic approaches and supports basic research efforts to characterise complex pathophysiological processes associated with mastitis. Furthermore, our data highlight the potential limitations of FCS in studies. Our data should not only stimulate the discussion about FCS in homologues or heterologues species, but should also be kept in mind regarding the need for foetal calves to generate FCS in line with the 3Rs guideline.
奶牛乳腺炎对健康构成重大挑战，并给乳制品行业带来巨大经济损失。本研究旨在扩展现有的精确切割牛乳房切片（PCBUS）模型，将其作为一种模型来探索在乳房中诱导训练性免疫的潜力，目的是将所得知识用于潜在的新治疗策略。有趣的是，将PCBUS与10%胎牛血清（FCS）孵育，但不与2%或无FCS孵育，会对所分析的一些趋化因子/细胞因子的产生产生负面影响。当用酵母聚糖诱导训练性免疫，随后用衍生的脂多糖（LPS）刺激时，白细胞介素（IL）-1β、IL-6、肿瘤坏死因子α和干扰素（IFNγ）的产生下调，而IL-17A和促分解脂质介质（白三烯和前列腺素）的产生上调。虽然当前的实验设置并未明确证实对PCBUS中分析的所有参数都诱导了训练性免疫，但它验证了PCBUS作为研究牛乳房炎症的强大模型的实用性。该模型为开发创新的乳腺炎治疗方法提供了一个有前景的平台，特别是考虑到对抗菌素耐药性的日益关注，以及符合3R原则为实验研究中使用活体动物提供替代方案。它还为增进我们对牛乳房免疫反应的理解提供了一个有价值的工具。通过将精确切割组织切片技术应用于牛乳房，该模型能够对新的治疗方法进行广泛研究，并支持基础研究工作，以表征与乳腺炎相关的复杂病理生理过程。此外，我们的数据突出了FCS在研究中的潜在局限性。我们的数据不仅应激发关于同源或异源物种中FCS的讨论，还应在根据3R指南需要胎牛来生产FCS方面加以考虑。
