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Gut microorganisms act together to exacerbate inflammation in spinal cords
Gut microorganisms act together to exacerbate inflammation in spinal cords
- Source :
- Nature. 585(7823)
- Publication Year :
- 2019
-
Abstract
- Accumulating evidence indicates that gut microorganisms have a pathogenic role in autoimmune diseases, including in multiple sclerosis1. Studies of experimental autoimmune encephalomyelitis (an animal model of multiple sclerosis)2,3, as well as human studies4-6, have implicated gut microorganisms in the development or severity of multiple sclerosis. However, it remains unclear how gut microorganisms act on the inflammation of extra-intestinal tissues such as the spinal cord. Here we show that two distinct signals from gut microorganisms coordinately activate autoreactive T cells in the small intestine that respond specifically to myelin oligodendrocyte glycoprotein (MOG). After induction of experimental autoimmune encephalomyelitis in mice, MOG-specific CD4+ T cells are observed in the small intestine. Experiments using germ-free mice that were monocolonized with microorganisms from the small intestine demonstrated that a newly isolated strain in the family Erysipelotrichaceae acts similarly to an adjuvant to enhance the responses of T helper 17 cells. Shotgun sequencing of the contents of the small intestine revealed a strain of Lactobacillus reuteri that possesses peptides that potentially mimic MOG. Mice that were co-colonized with these two strains showed experimental autoimmune encephalomyelitis symptoms that were more severe than those of germ-free or monocolonized mice. These data suggest that the synergistic effects that result from the presence of these microorganisms should be considered in the pathogenicity of multiple sclerosis, and that further study of these microorganisms may lead to preventive strategies for this disease.
- Subjects :
- 0301 basic medicine
Limosilactobacillus reuteri
Male
Encephalomyelitis, Autoimmune, Experimental
Multiple Sclerosis
Encephalomyelitis
T-Lymphocytes
Inflammation
Microbiology
Myelin oligodendrocyte glycoprotein
03 medical and health sciences
Mice
0302 clinical medicine
Intestine, Small
medicine
Animals
Germ-Free Life
Multidisciplinary
biology
Multiple sclerosis
Experimental autoimmune encephalomyelitis
medicine.disease
biology.organism_classification
Small intestine
Lactobacillus reuteri
Gastrointestinal Microbiome
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Spinal Cord
biology.protein
Experimental pathology
Th17 Cells
Female
Myelin-Oligodendrocyte Glycoprotein
medicine.symptom
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14764687
- Volume :
- 585
- Issue :
- 7823
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....cf328c9377ac4558d2f668a2b0076240