The secretomes of bovine mammary epithelial cell subpopulations differentially modulate macrophage function.

IF 7.9 2区 农林科学 Q1 VETERINARY SCIENCES
Veterinary Quarterly Pub Date : 2025-12-01 Epub Date: 2025-02-08 DOI:10.1080/01652176.2025.2463338
Nikola Danev, Rebecca M Harman, Anja S Sipka, Leanne Oliveira, Lucas Huntimer, Gerlinde R Van de Walle
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引用次数: 0

Abstract

Bovine mammosphere-derived epithelial cell (MDEC) cultures are heterogeneous and enriched for stem and progenitor cells. We previously reported that the bovine MDEC secretome, comprised of all bioactive factors secreted by the cells, displays regenerative properties, exerts antimicrobial effects, and modulates neutrophil activity, positioning it as a promising non-antibiotic biologic therapy for infectious diseases important to the dairy industry, like mastitis. Mastitis is defined as inflammation of the udder, and it is typically caused by bacterial infection. The effect of the MDEC secretome on macrophages, a first line of defense against bacterial infections in the udder, is unknown and could impact the utility of the secretome as a therapy for mastitis. To address this, we isolated bovine monocytes from peripheral blood and maintained them as an unpolarized (M0) population or polarized them into M1 or M2 phenotypes. Macrophages cultured with the secretome of bovine MDECs were assessed for their ability to phagocytose labeled bacterial particles and accumulate reactive oxygen species (ROS). We used single-cell RNA sequencing (scRNA-seq) and fluorescence-activated cell sorting (FACS) to isolate a subpopulation of MDECs that exert enhanced effects on macrophages. We found that the secretome of MDECs that do not express cluster of differentiation (CD) 73, a cell surface enzyme used as a marker for mesenchymal stromal cells, most strongly increased macrophage phagocytosis and ROS accumulation. These findings will help optimize the generation of the bovine MDEC secretome as a suitable treatment option for mastitis.

牛乳腺上皮细胞亚群分泌组差异调节巨噬细胞功能。
牛乳腺球源性上皮细胞(MDEC)培养是异质的,干细胞和祖细胞富集。我们之前报道了牛MDEC分泌组,由细胞分泌的所有生物活性因子组成,显示再生特性,发挥抗菌作用,并调节中性粒细胞活性,将其作为一种有前途的非抗生素生物疗法,用于治疗对乳业重要的感染性疾病,如乳腺炎。乳腺炎被定义为乳房的炎症,通常由细菌感染引起。MDEC分泌组对巨噬细胞的作用是未知的,巨噬细胞是抵抗乳房细菌感染的第一道防线,可能会影响分泌组作为乳腺炎治疗的效用。为了解决这个问题,我们从外周血中分离出牛单核细胞,并将其维持为未极化(M0)群体或极化为M1或M2表型。用牛MDECs分泌组培养巨噬细胞,评估其吞噬标记细菌颗粒和积累活性氧(ROS)的能力。我们使用单细胞RNA测序(scRNA-seq)和荧光活化细胞分选(FACS)分离出对巨噬细胞有增强作用的MDECs亚群。我们发现,不表达分化簇(cd73)(一种用作间充质基质细胞标记的细胞表面酶)的MDECs分泌组最强烈地增加了巨噬细胞吞噬和ROS积累。这些发现将有助于优化牛MDEC分泌组的产生,作为乳腺炎的合适治疗选择。
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来源期刊
Veterinary Quarterly
Veterinary Quarterly VETERINARY SCIENCES-
CiteScore
13.10
自引率
1.60%
发文量
18
审稿时长
>24 weeks
期刊介绍: Veterinary Quarterly is an international open access journal which publishes high quality review articles and original research in the field of veterinary science and animal diseases. The journal publishes research on a range of different animal species and topics including: - Economically important species such as domesticated and non-domesticated farm animals, including avian and poultry diseases; - Companion animals (dogs, cats, horses, pocket pets and exotics); - Wildlife species; - Infectious diseases; - Diagnosis; - Treatment including pharmacology and vaccination
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