Immunization With Bovine Milk Casein Results in Enteric Nervous System Pathology in a Mouse Model of Neuroinflammation.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) with evidence of autoimmune attack also on the enteric nervous system (ENS). The role of different dietary antigens, including bovine milk proteins, in the exacerbation of MS symptoms has previously been discussed. In a mouse model of neuroinflammation, we characterized the extent of ENS pathology in animals that were immunized with different bovine milk antigens using electron microscopy, immunohistochemistry, molecular biology, and cell culture as key methods. Our data demonstrate that immunization of mice with bovine milk casein resulted in ENS pathology, which is in line with our previous findings where casein-immunized mice also exhibited demyelination in the CNS. Furthermore, development of ENS pathology was most likely due to a combination of cellular and humoral factors, as confirmed by our observation of CD3+ T cell infiltration in the tunica muscularis and binding of serum antibodies from casein-immunized mice to glial cells in the myenteric plexus. The findings presented in this paper reflect that exposure to bovine casein can result in axolysis in the myenteric plexus possibly as a result of molecular mimicry and antibody cross-reactivity between casein and antigen(s) expressed by the ENS.