Ijaz Adil, Pols Noah, Abboud Kahlile Youssef, Rutten Victor P M G, Broere Femke, Schols Henk, Veldhuizen Edwin J A, Jansen Christine A
Division Infectious Diseases and Immunology, Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Center for Healthy Eating and Food Innovation (HEFI)- Maastricht University, Campus Venlo, the Netherlands.
Int J Biol Macromol. 2025 Jan;286:138344. doi: 10.1016/j.ijbiomac.2024.138344. Epub 2024 Dec 3.
The restrictions on excessive use of antimicrobials in the poultry industry have led to the search for alternative strategies including nutritional interventions to enhance gut health with the ultimate aim to prevent gut infections. Pectins as prebiotics have shown beneficial effects on gut health in humans and mice by improving the gut barrier function, altering the gut microbiota, and by modulating the gut immune response. However, little is known about immunomodulatory properties of pectins in chickens. The present in vitro study assessed the effect of three pectins (SPE6, SPE7, SPE8) differing in methyl esterification, on responsiveness of the chicken macrophage cell line HD11 cells and primary monocyte derived macrophage from the blood, through interaction with chicken TLRs. All three pectins increased gene expression of iNOS and IL10 in chicken macrophages. Differences in immunomodulatory activity between the three pectins were observed in other assays. The low methoxyl pectin (SPE8) interacted with TLR4 leading to the production of NO, but also to increased phagocytosis of E. coli, while high methoxyl pectins SPE6 and SPE7 did not activate TLR4. All three pectins were able to attenuate PAM3CSK4 induced activation of chicken macrophages as measured by decreased NO production and phagocytosis. Additional studies using ITC and flow cytometry suggest that the inhibiting properties of pectins (SPE6, SPE7) on macrophages are due to pectins occupying TLR2 and blocking PAM3CSK4 to activate chicken macrophages, whereas SPE8 actually binds to the TLR2 ligand and that way attenuates the PAM3CSK4 induced activation. Based on these immunomodulatory properties observed in this study, these pectins may in the future be suitable as feed additive for the treatment and prevention of inflammatory disorders in poultry.
家禽业对抗微生物药物过度使用的限制促使人们寻找替代策略，包括通过营养干预来增强肠道健康，最终目的是预防肠道感染。果胶作为益生元，通过改善肠道屏障功能、改变肠道微生物群和调节肠道免疫反应，已在人类和小鼠中显示出对肠道健康的有益影响。然而，关于果胶在鸡体内的免疫调节特性知之甚少。本体外研究评估了三种甲酯化程度不同的果胶（SPE6、SPE7、SPE8）通过与鸡Toll样受体（TLR）相互作用，对鸡巨噬细胞系HD11细胞和血液中初级单核细胞衍生巨噬细胞反应性的影响。所有三种果胶均增加了鸡巨噬细胞中诱导型一氧化氮合酶（iNOS）和白细胞介素10（IL10）的基因表达。在其他试验中观察到三种果胶之间免疫调节活性的差异。低甲氧基果胶（SPE8）与TLR4相互作用，导致一氧化氮的产生，同时也增加了对大肠杆菌的吞噬作用，而高甲氧基果胶SPE6和SPE7未激活TLR4。通过一氧化氮产生和吞噬作用的降低来衡量，所有三种果胶均能够减弱PAM3CSK4诱导的鸡巨噬细胞激活。使用等温滴定量热法（ITC）和流式细胞术的进一步研究表明，果胶（SPE6、SPE7）对巨噬细胞的抑制特性是由于果胶占据TLR2并阻断PAM3CSK4激活鸡巨噬细胞，而SPE8实际上与TLR2配体结合，从而减弱PAM3CSK4诱导的激活。基于本研究中观察到的这些免疫调节特性，这些果胶未来可能适合作为饲料添加剂用于治疗和预防家禽的炎症性疾病。
