Abstract
Human infections with the food-borne zoonotic pathogen Campylobacter jejuni are progressively rising and constitute serious global public health and socioeconomic burdens. Hence, application of compounds with disease-alleviating properties are required to combat campylobacteriosis and post-infectious sequelae. In our preclinical intervention study applying an acute C. jejuni induced enterocolitis model, we surveyed the anti-pathogenic and immune-modulatory effects of the octapeptide NAP which is well-known for its neuroprotective and anti-inflammatory properties. Therefore, secondary abiotic IL-10−/− mice were perorally infected with C. jejuni and intraperitoneally treated with synthetic NAP from day 2 until day 5 post-infection. NAP-treatment did not affect gastrointestinal C. jejuni colonization but could alleviate clinical signs of infection that was accompanied by less pronounced apoptosis of colonic epithelial cells and enhancement of cell regenerative measures on day 6 post-infection. Moreover, NAP-treatment resulted in less distinct innate and adaptive pro-inflammatory immune responses that were not restricted to the intestinal tract but could also be observed in extra-intestinal and even systemic compartments. NAP-treatment further resulted in less frequent translocation of viable pathogens from the intestinal tract to extra-intestinal including systemic tissue sites. For the first time, we here provide evidence that NAP application constitutes a promising option to combat acute campylobacteriosis.
Highlights
Human campylobacteriosis cases that are mainly caused by the zoonotric pathogens Campylobacter jejuni and C. coli are progressively rising worldwide [1,2]
The course of the disease is self-limited and symptoms resolve within two weeks, but post-infectious complications such as Guillain-Barré syndrome (GBS), reactive arthritis, and chronic inflammatory morbidities in the intestinal tract might occur in rare instances [9,10,11]
Given that information regarding potential health-beneficial effects of NAP in infectious intestinal morbidities are lacking to date, we assessed the anti-pathogenic, anti-apoptotic, cell-regenerative, and anti-inflammatory effects of the octapeptide in the intestinal tract following exogenous NAP application to secondary abiotic IL-10−/− mice suffering from acute C. jejuni induced enterocolitis in frame of our present preclinical intervention study
Summary
Human campylobacteriosis cases that are mainly caused by the zoonotric pathogens Campylobacter jejuni and C. coli are progressively rising worldwide [1,2]. Our very recent pre-clinical intervention trials applying this clinical enterocolitis model mimicking key features of human campylobacteriosis revealed that defined dietary molecules such as carvacrol (abundant in thyme oil and oregano, for instance), and distinct vitamins including vitamin C and vitamin D could effectively alleviate C. jejuni induced disease due to their anti-apoptotic, cell-regenerative, and immune-modulatory (i.e., anti-inflammatory) properties [18,19,20]. Given that information regarding potential health-beneficial effects of NAP in infectious intestinal morbidities are lacking to date, we assessed the anti-pathogenic, anti-apoptotic, cell-regenerative, and anti-inflammatory effects of the octapeptide in the intestinal tract (and beyond) following exogenous NAP application to secondary abiotic IL-10−/− mice suffering from acute C. jejuni induced enterocolitis in frame of our present preclinical intervention study
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