Department of Pathobiology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 268, CH-8057 Zurich, Switzerland.
Pathog Dis. 2020 Aug 1;78(6). doi: 10.1093/femspd/ftaa040.
Chlamydia suis intestinal infection of single-animal experimental groups of gnotobiotic newborn piglets was previously reported to cause severe, temporary small intestinal epithelium damage. We investigated archived intestinal samples for pro-inflammatory nuclear factor kappa B (NF-κB) activation, Interleukin (IL)-6 and IL-8 production and immune cell influx. Samples were collected 2, 4 and 7 days post-inoculation with C. suis strain S45/6 or mock inoculum (control). Increased nuclear localization of epithelial NF-κB, representative of activation, in the jejunum and ileum of C. suis-infected animals, compared to uninfected controls, began by 2 days post-infection (dpi) and persisted through 7 dpi. Infected animals showed increased production of IL-8, peaking at 2 dpi, compared to controls. Infection-mediated CD45-positive immune cell influx into the jejunal lamina propria peaked at 7 dpi, when epithelial damage was largely resolved. Activation of NF-κB appears to be a key early event in the innate response of the unprimed porcine immune system challenged with C. suis. This results in an acute phase, coinciding with the most severe clinical symptoms, diarrhea and weight loss. Immune cells recruited shortly after infection remain present in the lamina propria during the recovery phase, which is characterized by reduced chlamydial shedding and restored intestinal epithelium integrity.
先前的研究报道，猪源沙眼衣原体（Chlamydia suis）对单只无菌新生仔猪的肠道感染可导致严重且短暂的小肠上皮损伤。本研究对存档的肠道样本进行了检测，以研究促炎核因子 kappa B（NF-κB）的激活、白细胞介素（IL）-6 和 IL-8 的产生以及免疫细胞浸润情况。采集无菌新生仔猪在感染猪源沙眼衣原体 S45/6 株或模拟接种（对照）后的第 2、4 和 7 天的肠道样本。与对照组相比，感染动物空肠和回肠上皮 NF-κB 的核定位增加，表明其发生了激活，这种变化在感染后 2 天开始，并持续至 7 天。与对照组相比，感染动物的 IL-8 产生增加，在 2 天达到峰值。感染介导的 CD45 阳性免疫细胞浸润空肠固有层在 7 天达到峰值，此时上皮损伤基本得到修复。NF-κB 的激活似乎是未致敏猪固有免疫系统受到猪源沙眼衣原体挑战时的早期先天反应的关键事件。这导致了一个急性阶段，与最严重的临床症状（腹泻和体重减轻）同时发生。感染后不久被招募的免疫细胞在恢复阶段仍存在于固有层中，此时特征为脱落的衣原体减少和恢复的肠道上皮完整性。
