Abstract
Human Campylobacter 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 Campylobacter jejuni 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 C. jejuni 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 C. jejuni 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.
Highlights
Campylobacter jejuni constitute major infectious bacterial agents of zoonotic enteric morbidities with increasing prevalences worldwide [1]
Secondary abiotic IL-10−/− mice were subjected to synthetic 25-OH-cholecalciferol treatment via the drinking water starting 4 days before C. jejuni infection
Cultural analyses of fecal samples revealed that 25-OH-cholecalciferol application did not affect pathogenic intestinal colonization properties as indicated by stable median fecal C. jejuni loads of 109 colony-forming units (CFU)/g over time p.i. that did not differ between both cohorts at respective time points (n.s.; Figure S1)
Summary
Campylobacter jejuni constitute major infectious bacterial agents of zoonotic enteric morbidities with increasing prevalences worldwide [1]. Infected individuals present with symptoms of varying degree depending on the virulence of the acquired bacterial strain on one side and the host immune status on the other [1, 5,6,7]. Some patients display rather mild symptoms including watery diarrhea, whereas others develop acute campylobacteriosis [8, 9]. These severely compromised individuals complain about abdominal cramps, fever, and inflammatory bloody diarrhea [8, 9]. Postinfectious sequelae such as Guillain-Barré syndrome, Miller Fisher syndrome, Reiter’s syndrome, and reactive arthritis might arise with a latency of weeks to months [8, 9, 12]
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