Multiple sclerosis (MS) is an inflammatory disease of the CNS. In this issue of the JCI, Ma and Sannino et al. show that two strains of intestinal Clostridium perfringens, known to produce epsilon toxin (ETX), were frequently found in patients with MS. Tiny amounts of this toxin added to immunization with myelin antigens provoked MS-like brain lesions in mice. The distribution of these lesions was diffuse, as in MS, in contrast to the spinal cord-restricted lesions of most animal models. ETX bound to endothelial cells of the CNS to enhance immune cell trafficking through the blood-brain barrier into inflammatory brain lessons. ETX also binds to human, but not murine, white blood cells, perhaps altering immune responses. Barrier disruption and changes in immunity due to the toxin could alter the benefits of immune-modulatory MS therapies and are likely to interact with the complex genetics and environmental influences seen in MS.
Keyphrases
- multiple sclerosis
- white matter
- escherichia coli
- mass spectrometry
- endothelial cells
- ms ms
- spinal cord
- immune response
- oxidative stress
- induced apoptosis
- blood brain barrier
- spinal cord injury
- mouse model
- dendritic cells
- magnetic resonance
- type diabetes
- skeletal muscle
- inflammatory response
- cell proliferation
- adipose tissue
- toll like receptor
- signaling pathway
- metabolic syndrome
- risk assessment
- high glucose