Oral treatment with enrofloxacin creates anti-inflammatory environment that supports induction of tolerogenic dendritic cells.

BACKGROUND: Oral enrofloxacin treatment altered the gut microbiome promoting anti-inflammatory bacteria. The dysbiosis promotes regulatory cell induction in the intestines and in the periphery, which suppresses contact sensitivity. Bacterial-derived signals promote regulatory cell induction both directly and indirectly by influencing the phenotype of dendritic cells (DC). METHODS: Oral treatment with broad-spectrum antibiotic enrofloxacin was used to evaluate how gut flora perturbation shapes the immune response in the gut and the periphery. RESULTS: Enrofloxacin-induced dysbiosis creates an anti-inflammatory environment characterized by increased IL-10 concentration in the gut lumen and tissues. The production of IFN-γ and IL-17A did not change. Oral enrofloxacin treatment skewed the profile of the immune response towards an anti-inflammatory phenotype locally in small intestinal Peyer's Patches (PP) and systematically in the spleen (SPL). Enrofloxacin administration changed immune response in PP by increasing TGF-ß secretion from an increased percentage of TGF-ß-producing. In the SPL, enrofloxacin treatment increased the secretion of TGF-ß and IL-10 and decreased the secretion of IL-17A and IFN-γ. The shift in cytokine profile correlated with a higher percentage of latency-associated peptide and IL-10-producing cells and a decreased percentage of IFN-γ-producing T cells. This anti-inflammatory immune response in the PP and SPL promoted a higher frequency of tolerogenic DC. CONCLUSION: Our data indicate that two-week enrofloxacin treatment induces dysbiosis, skews immune response towards an anti-inflammatory phenotype, and elevates secretion of TGF-ß and IL-10 in the intestines and periphery. Additionally, we observed higher frequencies of tolerogenic DC, characterized by CD11b and IL-10 expression, which are known inducers of Treg cells.

Oral treatment with enrofloxacin early in life promotes Th2-mediated immune response in mice.

BACKGROUND: Th2 lymphocytes play a crucial role in the development of allergy. These pathologies are caused by coordinated production of the cytokines IL-4, IL-5 and IL-13 that regulate the activity of eosinophils, basophils and B cells. According to the 'hygiene hypothesis', the reduced exposure to microorganisms favors allergy occurrence. The advances in medicine in the field of infection therapy promoted an increasing application of antibiotics which, apart from eliminating pathogens, also partially eliminate the microbiota. METHODS: Epicutaneous (EC) immunization with ovalbumin (OVA) followed by OVA challenge was used to study the influence of partial gut flora depletion by oral treatment with enrofloxacin on type-2 immune response. RESULTS: Current work describes the influence of enrofloxacin application on anti-OVA antibody production and cytokine synthesis in young and adult mice. Immune response in adult mice is less sensitive to modification of natural gut flora. We observed that enrofloxacin treatment of adult mice leads to significant decrease of anti-OVA IgG2a production while synthesis of anti-OVA IgE was not changed. The production of type-1 (IFN-γ), type-2 (IL-4, IL-5, IL-10, IL-13) and Th17-associated (IL-17A) cytokines was inhibited. On the other hand, treatment of young mice with enrofloxacin significantly upregulates the production of anti-OVA IgE and inhibits the secretion of anti-OVA IgG2a antibodies. Additionally, treatment with enrofloxacin early in life prior to OVA immunization results in increased production of type-2 (IL-4, IL-10 and IL-13) cytokines. CONCLUSION: Our results clearly indicate that the immune system is more vulnerable to decreased bacterial exposure early in life that may promote development of allergy.