Institute of Microbiology, Infectious Diseases and Immunology, Charité - University Medicine Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Institute of Clinical Physiology, Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Front Immunol. 2019 Sep 3;10:2094. doi: 10.3389/fimmu.2019.02094. eCollection 2019.
Human infections are progressively rising and of high socioeconomic impact. In the present preclinical intervention study we investigated anti-pathogenic, immuno-modulatory, and intestinal epithelial barrier preserving properties of vitamin D applying an acute campylobacteriosis model. Therefore, secondary abiotic IL-10 mice were perorally treated with synthetic 25-OH-cholecalciferol starting 4 days before peroral infection. Whereas, 25-OH-cholecalciferol application did not affect gastrointestinal pathogen loads, 25-OH-cholecalciferol treated mice suffered less frequently from diarrhea in the midst of infection as compared to placebo control mice. Moreover, 25-OH-cholecalciferol application dampened induced apoptotic cell responses in colonic epithelia and promoted cell-regenerative measures. At day 6 post-infection, 25-OH-cholecalciferol treated mice displayed lower numbers of colonic innate and adaptive immune cell populations as compared to placebo controls that were accompanied by lower intestinal concentrations of pro-inflammatory mediators including IL-6, MCP1, and IFN-γ. Remarkably, as compared to placebo application synthetic 25-OH-cholecalciferol treatment of infected mice resulted in lower cumulative translocation rates of viable pathogens from the inflamed intestines to extra-intestinal including systemic compartments such as the kidneys and spleen, respectively, which was accompanied by less compromised colonic epithelial barrier function in the 25-OH-cholecalciferol as compared to the placebo cohort. In conclusion, our preclinical intervention study provides evidence that peroral synthetic 25-OH-cholecalciferol application exerts inflammation-dampening effects during acute campylobacteriosis.
人类感染的病例逐渐增多，对社会经济的影响也很大。在本临床前干预研究中，我们应用急性弯曲杆菌病模型，研究了维生素 D 的抗病原体、免疫调节和维持肠道上皮屏障的特性。因此，我们对继发无菌性 IL-10 缺陷的小鼠进行了口服补充合成的 25-OH-胆钙化醇，在口服感染前 4 天开始治疗。然而，25-OH-胆钙化醇的应用并没有影响胃肠道病原体的负荷，与安慰剂对照组相比，25-OH-胆钙化醇治疗的小鼠在感染过程中腹泻的频率较低。此外，25-OH-胆钙化醇的应用减轻了诱导的结肠上皮细胞凋亡反应，并促进了细胞再生措施。在感染后第 6 天，与安慰剂对照组相比，25-OH-胆钙化醇治疗的小鼠结肠固有和适应性免疫细胞群体数量较少，这伴随着肠道中促炎介质（包括 IL-6、MCP1 和 IFN-γ）的浓度降低。值得注意的是，与安慰剂应用相比，合成的 25-OH-胆钙化醇治疗感染小鼠导致从发炎的肠道向包括肾脏和脾脏等系统隔室的可存活病原体的累积易位率降低，这与 25-OH-胆钙化醇组相比，结肠上皮屏障功能的损害程度较低。总之，我们的临床前干预研究提供了证据，表明口服补充合成的 25-OH-胆钙化醇在急性弯曲杆菌病期间具有抗炎作用。
