Conventional housing conditions attenuate the development of experimental autoimmune encephalomyelitis
Andreas Arndt1, Peter Hoffacker1, Konstantin Zellmer1
1Department of Anatomy I, University of Cologne, Cologne, Germany.
Background:
The 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.
Methods:
C57BL/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.
Results:
In 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.
Conclusions:
The 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.
Insights
Gut bacteria may reduce the severity of experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS). Conventional housing, with gut microbes, attenuated EAE in mice compared to germ-free conditions.
Area of Science:
- Immunology
- Neuroscience
- Microbiology
Background:
- The exact cause of multiple sclerosis (MS) is unknown, but external factors like gut bacteria may play a role.
- Gut microbes might activate T cells that attack the central nervous system (CNS), leading to demyelination.
Purpose of the Study:
- To investigate the impact of housing conditions and gut microbiota on the development of experimental autoimmune encephalomyelitis (EAE) in mice.
- To explore the relationship between gut bacteria, immune responses, and demyelinating disease.
Main Methods:
- C57BL/6 mice were housed in specific pathogen-free (SPF) or conventional conditions.
- Mice were immunized with the MP4 fusion protein to induce EAE.
- Immune responses, germinal center size, and IgG secretion were assessed using ELISPOT and immunohistochemistry.
- Delayed-type hypersensitivity (DTH) was measured via ear swelling assays.
Main Results:
- Conventional housing significantly attenuated clinical EAE compared to SPF conditions.
- Conventionally housed mice showed increased IgG secretion but diminished germinal center formation and MP4-specific TH17 responses.
- DTH reactions were reduced in conventionally housed mice.
Conclusions:
- Housing conditions, specifically the presence of gut bacteria, influence EAE induction.
- Gut microbiota may be associated with reduced immune responses to certain antigens.
- Findings suggest potential implications for MS pathogenesis and antibiotic therapies.
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