MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China.
Vet Res. 2023 Jan 30;54(1):7. doi: 10.1186/s13567-023-01135-3.
Streptococcus suis serotype 2 (SS2) frequently colonizes the swine upper respiratory tract and can cause Streptococcal disease in swine with clinical manifestations of pneumonia, meningitis, and septicemia. Previously, we have shown that vimentin, a kind of intermediate filament protein, is involved in the penetration of SS2 through the tracheal epithelial barrier. The initiation of invasive disease is closely related to SS2-induced excessive local inflammation; however, the role of vimentin in airway epithelial inflammation remains unclear. Here, we show that vimentin deficient mice exhibit attenuated lung injury, diminished production of proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and the IL-8 homolog, keratinocyte-derived chemokine (KC), and substantially reduced neutrophils in the lungs following intranasal infection with SS2. We also found that swine tracheal epithelial cells (STEC) without vimentin show decreased transcription of IL-6, TNF-α, and IL-8. SS2 infection caused reassembly of vimentin in STEC, and pharmacological disruption of vimentin filaments prevented the transcription of those proinflammatory cytokines. Furthermore, deficiency of vimentin failed to increase the transcription of nucleotide oligomerization domain protein 2 (NOD2), which is known to interact with vimentin, and the phosphorylation of NF-κB protein p65. This study provides insights into how vimentin promotes excessive airway inflammation, thereby exacerbating airway injury and SS2-induced systemic infection.
猪链球菌 2 型（SS2）常定植于猪上呼吸道，可引起猪的链球菌病，临床表现为肺炎、脑膜炎和败血症。此前，我们已经证明，中间丝蛋白波形蛋白参与了 SS2 通过气管上皮屏障的穿透。侵袭性疾病的发生与 SS2 诱导的过度局部炎症密切相关；然而，波形蛋白在气道上皮炎症中的作用尚不清楚。在这里，我们发现波形蛋白缺陷小鼠在鼻腔感染 SS2 后，肺损伤减轻，促炎细胞因子白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和 IL-8 同系物角质形成细胞衍生趋化因子（KC）的产生减少，肺部中性粒细胞明显减少。我们还发现，缺乏波形蛋白的猪气管上皮细胞（STEC）中 IL-6、TNF-α 和 IL-8 的转录减少。SS2 感染导致 STEC 中波形蛋白的重新组装，而波形蛋白丝的药理学破坏阻止了这些促炎细胞因子的转录。此外，波形蛋白的缺乏未能增加核苷酸寡聚化结构域蛋白 2（NOD2）的转录，NOD2 已知与波形蛋白相互作用，以及 NF-κB 蛋白 p65 的磷酸化。这项研究提供了一些见解，即波形蛋白如何促进过度的气道炎症，从而加重气道损伤和 SS2 诱导的全身感染。
