Iron Deprivation by Oral Deferoxamine Application Alleviates Acute Campylobacteriosis in a Clinical Murine Campylobacter jejuni Infection Model.

Biomolecules(2022)

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摘要
The progressively rising food-borne infections pose serious health problems and socioeconomic burdens. Given that antibiotic therapy is not recommended for most campylobacteriosis patients, novel treatment options include strategies targeting iron homeostasis that impacts both virulence and inflammatory cell damage caused by toxic oxygen species. In our preclinical intervention study, we tested potential disease-alleviating effects upon prophylactic oral application of the iron-chelating compound desferoxamine (DESF) in acute murine campylobacteriosis. Therefore, microbiota-depleted IL-10 mice received synthetic DESF via the drinking water starting seven days before oral infection with strain 81-176. Results revealed that the DESF application did not reduce gastrointestinal pathogen loads but significantly improved the clinical outcome of infected mice at day 6 post-infection. This was accompanied by less pronounced colonic epithelial cell apoptosis, attenuated accumulation of neutrophils in the infected large intestines and abolished intestinal IFN-γ and even systemic MCP-1 secretion. In conclusion, our study highlights the applied murine campylobacteriosis model as suitable for investigating the role of iron in infection in vivo as demonstrated by the disease-alleviating effects of specific iron binding by oral DESF application in acute induced enterocolitis.
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关键词
Campylobacter jejuni,acute campylobacteriosis model,desferoxamine,disease-modifying properties,enteropathogenic infection,host-pathogen interaction,immune-modulatory effects,iron binding,microbiota-depleted IL-10−/− mice,natural antibiotics-independent compounds,preclinical intervention study,reactive oxygen species
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