Possible link between viral infections in children and multiple sclerosis

A potential link between neurological viral infections and the risk of developing autoimmune diseases in adulthood discovered.

Mice-model experiment observed an accumulation of bTRM cells, following a viral infection

A potential link between neurological viral infections and the risk of developing autoimmune diseases in adulthood discovered.

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Although the exact causes of multiple sclerosis remain unknown, it is assumed that the disease is triggered by a combination of genetic and environmental risk factors. The results of recent Swiss research published in the journal Science Translational Medicine are a first step towards determining one of the possible environmental causes of this serious disease.

Multiple sclerosis is the most common autoimmune disease affecting the brain. To date, there is no available treatment or a clear understanding of the factors that cause it. "We wondered whether neurological viral infections acquired in early childhood are among the possible causes," said Prof. Doron Merkler, from the Department of Pathology and Immunology at the Faculty of Medicine, University of Geneva. Switzerland. Such transient infections can be quickly controlled by the immune system, without the affected individual noticing symptoms. "But these transient infections can, under certain circumstances, leave an imprint in the brain," he added.

To test this hypothesis, the researchers induced a transient viral infection in a group of adult mice and a group of young mice. In both cases, the mice showed no signs of the disease and overcame the infection within a week, with a similar immune response. Scientists then waited for the two groups of mice to age. They then transferred self-reactive cells to their organisms. These cells are believed to play a role in the development of multiple sclerosis. Self-reactive cells are present in most of us but do not necessarily induce the disease, as they are controlled by different regulatory mechanisms. In the group of mice infected with the virus in adulthood, self-reactive cells have not passed the blood-brain barrier and no brain lesions have been observed. Instead, in those mice infected at a very young age, the self-reactive cells reached the brain and migrated to the precise location where the infection had previously occurred. As a result, the self-reactive cells began to attack the brain structure in these areas, leading to the development of brain lesions.

During brain analysis of the cohort of mice with viral infection at an early age, researchers observed an accumulation of a subtype of immune cells, the so-called brain-resident memory T cells (bTRM). "Under normal circumstances, these cells are distributed throughout the brain, ready to protect it in the event of a viral attack. But here the cells accumulate in excess at the exact point of the infant infection," said Professor Merkler. Researchers subsequently discovered that these cells produce a molecule that specifically attracts self-reactive cells, allowing them to access the brain and cause autoimmune brain damage. By analogy, scholars hypothesize that self-reactive T cells in humans could have access to the brain through a mechanism similar to that observed in mice. Researchers intend to continue research in this direction.

1. Steinbach K, Vincenti I, Egervari K, Kreutzfeldt M, van der Meer F, Page N, Klimek B, Rossitto-Borlat I, Di Liberto G, Muschaweckh A, Wagner I, Hammad K, Stadelmann C, Korn T, Hartley O, Pinschewer DD, Merkler D. Brain-resident memory T cells generated early in life predisposed to autoimmune disease in mice. Ski Transl Med. 2019 Jun 26;11(498). pii: eaav5519. doi: 10.1126/scitranslmed.aav5519.
2. Université de Genève Press Release. Is multiple sclerosis linked to childhood viral infections? June 26 2019