Vagus nerve stimulation dampens intestinal inflammation in a murine model of experimental food allergy

Abstract

Background The vagus nerve has emerged as an important modulator of the intestinal immune system. Its anti‐inflammatory properties have been previously shown in innate and Th1/Th17 predominant inflammatory models. To what extent the vagus nerve is of importance in Th2 inflammatory responses like food allergy is still unclear. In this study, we therefore aimed to investigate the effect of vagotomy (VGX) and vagus nerve stimulation (VNS), on the development and severity of experimental food allergy. Methods Balb/C mice were first sensitized with ovalbumin (OVA) in the presence of alum. Prior to oral challenges with OVA, mice were subjected to VGX or VNS. Disease severity was determined by assessing severity and onset of diarrhoea, OVA‐specific antibody production, mast cell number and activity, inflammatory gene expression in duodenal tissue and lamina propria immune cells by flow cytometry analysis. Results When compared to control mice, VGX did not significantly affect the development and severity of the disease in our model of food allergy. VNS, on the other hand, resulted in a significant amelioration of the different inflammatory parameters assessed. This effect was independent of α7nAChR and is possibly mediated through the dampening of mast cells and increased phagocytosis of OVA by CX3CR1hi macrophages. Conclusions These results underscore the anti‐inflammatory properties of the vagus nerve and the potential of neuro‐immune interactions in the intestine. Further insight into the underlying mechanisms could ultimately lead to novel therapeutic approaches in the treatment of not only food allergy but also other immune‐mediated diseases.

Lack of mucosal cholinergic innervation is associated with increased risk of enterocolitis in Hirschsprung’s disease

“…However, anti-inflammatory neuro-immune modulation seems to involve different neuronal receptors in type 2-mediated intestinal disease models. For example, in a murine model of food allergy, VN stimulation ameliorated disease severity independently of α7nAChR 74 . Uptake of food antigens by anti-inflammatory CX3CR1 + MΦ and subsequent induction of food-specific Tregs effectively prevent allergic reactions 44 .…”

Comparison between the cervical and abdominal vagus nerves in mice, pigs, and humans

“…VNS was indeed shown to exert an anti-inflammatory effect in a model of sepsis by modulation of macrophages via the α7 nicotinic acetylcholine receptor (α7nAChR). 4,5 Also in the gastrointestinal (GI) tract, we and others demonstrated that cervical VNS dampens macrophage activation in experimental colitis, 6,7 food allergy, 8 and postoperative ileus. 9,10 Interestingly, our group recently showed that electrical stimulation of both the subdiaphragmatic posterior and anterior vagal branches possesses similar anti-inflammatory properties as cervical VNS in mice 11,12 and thus could be used as an alternative approach for cervical VNS.…”

Peripheral neurons: Master regulators of skin and mucosal immune response

“…Vagotomy was shown to worsen inflammation in mouse models of colitis , independently of the α7 nicotinic acetylcholine receptors (α7nAChR) . On the contrary, vagus nerve stimulation (VNS) has been shown to improve local and systemic inflammation (i.e., reduced levels of inflammatory cytokines in the mucosa and serum) in mouse models of Th2 cells‐dependent colitis and food allergy . In addition, chronic electrical stimulation of the vagus nerve also ameliorated Trinitrobenzenesulfonic acid (TNBS)‐induced colitis in rats .…”