Conventional Housing Conditions Attenuate the Development of Experimental Autoimmune Encephalomyelitis

Abstract

BackgroundThe etiology of multiple sclerosis (MS) has remained unclear, but a causative contribution of factors outside the central nervous system (CNS) is conceivable. It was recently suggested that gut bacteria trigger the activation of CNS-reactive T cells and the development of demyelinative disease.MethodsC57BL/6 (B6) mice were kept either under specific pathogen free or conventional housing conditions, immunized with the myelin basic protein (MBP)–proteolipid protein (PLP) fusion protein MP4 and the development of EAE was clinically monitored. The germinal center size of the Peyer’s patches was determined by immunohistochemistry in addition to the level of total IgG secretion which was assessed by ELISPOT. ELISPOT assays were also used to measure MP4-specific T cell and B cell responses in the Peyer’s patches and the spleen. Ear swelling assays were performed to determine the extent of delayed-type hypersensitivity reactions in specific pathogen free and conventionally housed mice.ResultsIn B6 mice that were actively immunized with MP4 and kept under conventional housing conditions clinical disease was significantly attenuated compared to specific pathogen free mice. Conventionally housed mice displayed increased levels of IgG secretion in the Peyer’s patches, while the germinal center formation in the gut and the MP4-specific TH17 response in the spleen were diminished after immunization. Accordingly, these mice displayed an attenuated delayed type hypersensitivity (DTH) reaction in ear swelling assays.ConclusionsThe data corroborate the notion that housing conditions play a substantial role in the induction of murine EAE and suggest that the presence of gut bacteria might be associated with a decreased immune response to antigens of lower affinity. This concept could be of importance for MS and calls for caution when considering the therapeutic approach to treat patients with antibiotics.

Associations of childhood experiences with event-related potentials in adults with autism spectrum disorder

“…P300 latency is considered to be related to the interval between perception and reaction and to the monitoring process. Prolonged P300 latencies are associated with cognitive impairment in several psychiatric disorders such as schizophrenia 57 , 58 and Alzheimer’s disease 59 . Therefore, we suggest that adults with ASD have impairments in perception and reaction and monitoring process.…”

Wild immunology assessed by multidimensional mass cytometry

“…Therefore, SPF mice may not be able to serve as an ideal model for the natural functioning of immunity . Recently, it has been emphasized that differences in the colonization of SPF mice with commensals can already drastically change outcomes in experimental colitis and experimental autoimmune encephalomyelitis induction . Thus, it is to be expected that radically distinct outcomes may also emerge if mice are preemptively exposed to “natural” pathogens and then compared to unexposed SPF counterparts.…”

Genomic, microbial and environmental standardization in animal experimentation limiting immunological discovery

“…Autoimmune and chronic inflammatory diseases It is well known that the phenotype of different mouse models of autoimmune and chronic inflammatory diseases may be dramatically altered by changes in institution, housing conditions, and/or diet [74][75][76][77]. This is not surprising given the evidence demonstrating that the intestinal microbiota of mice may vary greatly among different animal care facilities and animal vendors [74,75,[78][79][80].…”