Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph N1G 2W1, ON, Canada.
Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph N1G 2W1, ON, Canada.
Cytokine. 2024 Nov;183:156749. doi: 10.1016/j.cyto.2024.156749. Epub 2024 Sep 4.
In humans and mice, the induction of interleukin (IL)-17 expression enhances epithelial barrier integrity through the secretion of antimicrobial peptides (AMP), thereby improving antibacterial defense. However, it is unclear whether IL-17 has similar antibacterial effects in chickens by modulating the expression of AMPs, such as avian beta-defensins (also known as gallinacins) and cathelicidins. This study evaluated the in vivo effects of inoculating 20-day-old broiler chickens with two doses of a plasmid encoding chicken IL-17 (pCDNA3.1/rchIL-17-V5-HIS TOPO plasmid [pCDNA3.1-IL-17]; 5 or 10 μg/bird). On day 23 of age, all broilers, except those in the negative control group, were orally challenged with a virulent Clostridium perfringens strain for three days. To investigate IL-17-mediated effects against C. perfringens infection, the expression of avian beta-defensin 1 (avBD1), avBD2, avBD4, avBD6, cathelicidins, and inducible nitric oxide synthase (iNOS) genes were quantified, and gross necrotic enteritis (NE) lesion scores were assessed in the small intestine. The results showed that broilers receiving the higher dose of pCDNA3.1-IL-17 (10 μg) had significantly lower NE lesion scores compared to those receiving the lower dose (5 μg), the vector control, and the positive control groups. Furthermore, the expression of all avian beta-defensins and cathelicidin genes was detectable across all groups, regardless of treatment and time points. IL-17 treatment led to significantly higher expression of avBD1, avBD2, avBD4, avBD6, cathelicidin, and iNOS in the duodenum, jejunum, and ileum compared to control chickens. In C. perfringens-infected chickens, the expression of avBD1, avBD2, avBD4, cathelicidin, and iNOS in the ileum was significantly higher than in control chickens. Pre-treatment with the higher dose of pCDNA3.1-IL-17 (10 μg) in infected chickens was associated with reduced NE lesion severity and increased expression of avBD1, avBD2, cathelicidin, and iNOS in the ileum, but not avBD4 and avBD6. These findings provide new insights into the potential effect of IL-17 and reduction in NE lesion severity by modulating AMP expression which may be involved in mediating protective immunity against intestinal infection with C. perfringens.
在人类和小鼠中，白细胞介素 (IL)-17 的诱导增强了上皮屏障的完整性，通过分泌抗菌肽 (AMP)，从而提高了抗菌防御能力。然而，目前尚不清楚 IL-17 是否通过调节 AMP 的表达（如禽类β-防御素（也称为 gallinacins）和 cathelicidins）在鸡中具有类似的抗菌作用。本研究评估了在 20 日龄肉鸡中接种两种剂量编码鸡白细胞介素 17 的质粒（pCDNA3.1/rchIL-17-V5-HIS TOPO 质粒 [pCDNA3.1-IL-17]；5 或 10μg/羽）的体内效果。在 23 日龄时，除阴性对照组外，所有肉鸡均连续 3 天经口感染强毒梭状芽孢杆菌。为了研究 IL-17 对梭状芽孢杆菌感染的介导作用，定量检测了禽类β-防御素 1 (avBD1)、avBD2、avBD4、avBD6、cathelicidins 和诱导型一氧化氮合酶 (iNOS)基因的表达，并评估了小肠的坏死性肠炎 (NE) 病变评分。结果表明，与接受较低剂量 (5μg)、载体对照和阳性对照组相比，接受较高剂量 (10μg) pCDNA3.1-IL-17 的肉鸡的 NE 病变评分显著降低。此外，所有禽类β-防御素和 cathelicidin 基因的表达在所有组中均有检测到，无论治疗和时间点如何。与对照鸡相比，IL-17 处理可显著提高十二指肠、空肠和回肠中 avBD1、avBD2、avBD4、avBD6、cathelicidin 和 iNOS 的表达。在感染梭状芽孢杆菌的鸡中，与对照鸡相比，回肠中 avBD1、avBD2、avBD4、cathelicidin 和 iNOS 的表达显著升高。在感染鸡中预先用较高剂量的 pCDNA3.1-IL-17（10μg）处理可减轻 NE 病变严重程度，并增加回肠中 avBD1、avBD2、cathelicidin 和 iNOS 的表达，但 avBD4 和 avBD6 的表达没有增加。这些发现为 IL-17 通过调节 AMP 表达减轻 NE 病变严重程度提供了新的见解，这可能涉及介导对梭状芽孢杆菌感染的肠道的保护性免疫。
