Kameli Nader, Becker Heike E F, Jonkers Daisy M, Penders John, Savelkoul Paul, Stassen Frank
Department of Medical Microbiology, College of Nursing and Health Sciences, Jazan University, Jazan 6809, Saudi Arabia.
Health Research Center, Jazan Univesiry, Jazan 6809, Saudi Arabia.
Int J Mol Sci. 2024 Dec 8;25(23):13194. doi: 10.3390/ijms252313194.
The human intestinal tract contains trillions of bacteria that coexist in a symbiotic relationship with human cells. Imbalances in this interaction can lead to disorders such as Crohn's disease (CD). Bacteria membrane vesicles (MVs), which are released by almost all bacteria, have been demonstrated to play a crucial role in bacteria-host interactions. In this study, we assessed the physical characterizations, immunomodulatory effects, and IgA interactions of MVs derived from fecal samples of CD patients and healthy controls (HCs). MVs were isolated from the frozen fecal samples using a combination of ultrafiltration and size-exclusion chromatography. Using nanoparticle tracking analysis, we found that the MVs of the CD patients showed a significantly lower concentration compared to those of the HCs. Cryo-transmission electron microscopy revealed the larger size of the MVs in active CD (Ac-CD) compared to the MVs of remission CD (Re-CD) and HCs. Differentiated monocyte THP-1 cells released more TNF-a when exposed to MVs from the HCs compared to the CD patients. On the other hand, the MVs from the HCs and Re-CD patients but not the Ac-CD patients induced more anti-inflammatory IL-10. Intriguingly, bead-based flow cytometry analysis showed that the MVs of the HCs and Re-CD patients were more coated with IgA compared to those of the Ac-CD patients. These results suggest the potential role of MVs in the immunomodulatory impact on the pathophysiology of CD. Moreover, IgA seems to regulate these effects by direct binding, which was not the case for the Ac-CD patients. Finally, the IgA coating patterns of the MVs could be used as an additional disease biomarker, as they can clearly identify the exacerbation status of CD.
人类肠道中含有数万亿细菌，它们与人类细胞以共生关系共存。这种相互作用的失衡会导致诸如克罗恩病（CD）等疾病。几乎所有细菌都会释放细菌膜泡（MVs），已证明其在细菌与宿主的相互作用中起关键作用。在本研究中，我们评估了来自CD患者和健康对照（HCs）粪便样本的MVs的物理特性、免疫调节作用及与IgA的相互作用。使用超滤和尺寸排阻色谱相结合的方法从冷冻粪便样本中分离出MVs。通过纳米颗粒跟踪分析，我们发现CD患者的MVs浓度明显低于HCs。冷冻透射电子显微镜显示，与缓解期CD（Re-CD）患者和HCs的MVs相比，活动期CD（Ac-CD）患者的MVs尺寸更大。与CD患者的MVs相比，分化的单核细胞THP-1细胞在暴露于HCs的MVs时释放更多的肿瘤坏死因子-α（TNF-α）。另一方面，HCs和Re-CD患者而非Ac-CD患者的MVs诱导产生更多的抗炎性白细胞介素-10（IL-10）。有趣的是，基于磁珠的流式细胞术分析表明，与Ac-CD患者的MVs相比，HCs和Re-CD患者的MVs被IgA包被的程度更高。这些结果表明MVs在对CD病理生理学的免疫调节影响中具有潜在作用。此外，IgA似乎通过直接结合来调节这些作用，而Ac-CD患者并非如此。最后，MVs的IgA包被模式可作为一种额外的疾病生物标志物，因为它们能够清晰地识别CD的病情加重状态。
