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围产期蛋氨酸和胆碱供应改变荷斯坦奶牛嗜中性白细胞免疫反应和免疫代谢基因表达。

Methionine and choline supply during the peripartal period alter polymorphonuclear leukocyte immune response and immunometabolic gene expression in Holstein cows.

机构信息

Department of Animal and Veterinary Sciences, Clemson University, Clemson, SC 29634.

Department of Animal and Veterinary Sciences, Clemson University, Clemson, SC 29634.

出版信息

J Dairy Sci. 2018 Nov;101(11):10374-10382. doi: 10.3168/jds.2018-14972. Epub 2018 Aug 29.

Abstract

Polymorphonuclear leukocytes (PMNL) are the first responders upon pathogen invasion and hence play an important role in inflammatory and immune responses. Rumen-protected methionine (MET) and choline (CHOL) during the peripartal period affect the immune response and inflammatory status in dairy cows to different extents. We aimed to examine the effect of MET and CHOL supply on expression of genes regulating key PMNL functions and associations with whole-blood immune challenge. Thirty multiparous Holstein cows from a larger cohort randomly assigned from -21 to 30 d relative to parturition to a basal control (CON) diet, CON plus MET at a rate of 0.08% of dry matter, or CON plus CHOL at 60 g/d were used. Blood was sampled at -10, 7, and 30 d relative to parturition for inflammatory biomarker analyses and PMNL isolation. Neutrophil and monocyte phagocytosis and oxidative burst in vitro were assessed in whole blood at 1, 7, and 28 d. Although neutrophil and monocyte phagocytosis did not differ, oxidative burst in neutrophils and monocytes was greater in MET-supplemented cows relative to CON cows. Compared with CON, PMNL adhesion and migration-related genes (ITGAM, ITGB2, ITGA4) were downregulated in response to MET and CHOL. Expression of CADM1 and SELL was also lower in MET-supplemented cows compared with CON cows but not in CHOL cows. In contrast, compared with CON cows, the expression of ICAM1 was lower in CHOL but not MET cows. Similar to adhesion and migration-related genes, cows receiving MET- or CHOL-supplemented diets had lower expression of inflammation-related genes (IL1β, IL10RA, NFKB1, STAT3, TLR2). However, expression of IRAK1 and TLR4 was lower in MET- but not CHOL-supplemented cows. Plasma taurine concentration was greater in MET cows compared with CHOL and CON cows, suggesting a better redox status in plasma. In agreement with plasma taurine, oxidative stress-related genes (CBS, CTH, GPX1, GSS, SOD2) in PMNL were lower in response to MET and to CHOL supply. Overall, immunometabolic gene expression profile and blood biomarker analyses suggest an overall better redox status in PMNL during the transition period in response to MET and CHOL supply. These adaptations in PMNL might be beneficial for mounting a better bactericidal response upon challenge.

摘要

多形核白细胞 (PMNL) 是病原体入侵时的第一反应者,因此在炎症和免疫反应中发挥着重要作用。围产期保护性蛋氨酸 (MET) 和胆碱 (CHOL) 对奶牛的免疫反应和炎症状态有不同程度的影响。我们旨在研究 MET 和 CHOL 供应对调节关键 PMNL 功能的基因表达的影响及其与全血免疫挑战的关联。

从更大的队列中随机选择 30 头经产荷斯坦奶牛,从分娩前 -21 天到 30 天分为基础对照 (CON) 饮食组、CON 加 MET(占干物质的 0.08%)组或 CON 加 CHOL(60g/d)组。在分娩前 -10、7 和 30 天采集血液进行炎症生物标志物分析和 PMNL 分离。在第 1、7 和 28 天,在全血中评估中性粒细胞和单核细胞的吞噬作用和氧化爆发。

虽然中性粒细胞和单核细胞的吞噬作用没有差异,但与 CON 牛相比,MET 补充牛的中性粒细胞和单核细胞的氧化爆发更大。与 CON 相比,PMNL 黏附和迁移相关基因 (ITGAM、ITGB2、ITGA4) 的表达在 MET 和 CHOL 作用下下调。与 CON 牛相比,CADM1 和 SELL 的表达在 MET 补充牛中也较低,但在 CHOL 牛中则没有。相比之下,与 CON 牛相比,CHOL 而不是 MET 牛的 ICAM1 表达较低。

与黏附和迁移相关基因类似,接受 MET 或 CHOL 补充饮食的奶牛的炎症相关基因 (IL1β、IL10RA、NFKB1、STAT3、TLR2) 表达较低。然而,只有在 MET 补充牛中,IRAK1 和 TLR4 的表达较低,而在 CHOL 补充牛中则没有。与 CHOL 和 CON 牛相比,MET 牛的血浆牛磺酸浓度更高,表明血浆中的氧化还原状态更好。与血浆牛磺酸一致,PMNL 中的氧化应激相关基因 (CBS、CTH、GPX1、GSS、SOD2) 的表达对 MET 和 CHOL 的供应有反应。

总之,免疫代谢基因表达谱和血液生物标志物分析表明,在 MET 和 CHOL 供应的情况下,过渡期 PMNL 的氧化还原状态总体更好。这些 PMNL 的适应性变化可能有利于在受到挑战时产生更好的杀菌反应。

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