MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, PR China.
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, PR China.
Res Vet Sci. 2020 Jun;130:179-183. doi: 10.1016/j.rvsc.2020.03.008. Epub 2020 Mar 3.
S. Pullorum is a causative agent of enteric disease of poultry with serious diarrhea. However, the detailed mechanism behind its injury to intestinal mucosa barrier, especially for intestinal stem cells, is unclear. In this study, S. Pullorum were orally administrated to 3 days old chicken to investigate the pathogenesis of S. Pullorum on intestinal mucosal barrier, especially on the proliferation of epithelial cells. We found that S. Pullorum could colonize in the cecum and invade into the liver through intestinal mucosa damage, which caused obvious pathological changes in liver and intestine and even leaded to death, as well as significant reduction of body weight. We also found that S. Pullorum infection enhanced the mRNA expression of IL-1β and IL-6 through TLR4/MyD88 pathway, which was also further verified by the increased lipopolysaccharide (LPS) levels in serum. Furthermore, S. Pullorum increased the depth of crypt and density of PCNA cells significantly through the over-activation of Wnt/β-catenin signaling pathway. The expression of intestinal stem cells markers Lgr5 and Bmi1 was also increased after S. Pullorum infection to support the crypt hyperplasia. In addition, we verified that S. Pullorum infection enhanced the mRNA expression of IL-1β, TLR4, Lgr5 and Bmi1. Our study indicated that S. Pullorum infection damaged the intestinal mucosa barrier to induce diarrhea, affected the abnormal proliferation of intestinal stem cells by over-activation of Wnt/β-catenin pathway in chicken.
鸡白痢是一种引起家禽肠道疾病的病原体，其特征为严重腹泻。然而，其损伤肠道黏膜屏障的详细机制，特别是对肠道干细胞的损伤机制尚不清楚。在本研究中，通过口灌服鸡白痢沙门氏菌感染 3 日龄雏鸡，研究其对肠道黏膜屏障，特别是对上皮细胞增殖的影响。我们发现，鸡白痢沙门氏菌可以通过破坏肠道黏膜在盲肠中定植，并通过肠黏膜损伤侵袭肝脏，导致肝脏和肠道明显的病理变化，甚至导致死亡，并显著降低体重。我们还发现，鸡白痢沙门氏菌感染通过 TLR4/MyD88 通路增强了 IL-1β 和 IL-6 的 mRNA 表达，这也被血清中脂多糖（LPS）水平的增加所进一步证实。此外，鸡白痢沙门氏菌通过过度激活 Wnt/β-catenin 信号通路，显著增加隐窝深度和 PCNA 细胞密度。感染后肠道干细胞标志物 Lgr5 和 Bmi1 的表达也增加，以支持隐窝增生。此外，我们还验证了鸡白痢沙门氏菌感染增强了 IL-1β、TLR4、Lgr5 和 Bmi1 的 mRNA 表达。本研究表明，鸡白痢沙门氏菌感染破坏了肠道黏膜屏障，引起腹泻，并通过过度激活 Wnt/β-catenin 通路，影响了肠道干细胞的异常增殖。
