New insight into autoimmune disease: Bacterial infections promote recognition of self-glycolipids

The immune system is a complex and powerful weapon that provides protection against bacteria and viruses that, if left unchecked, would wreak havoc throughout the human body. The ability of the immune system to recognize the body’s own tissues is essential, but sometimes the immune system loses the ability to distinguish “self” from potentially harmful invaders. This can lead to autoimmune disease characterized by destruction of healthy tissues. Although it is not clear exactly what causes the immune system to go awry, there is increasing evidence that in some cases infections with viruses or bacteria may play a role. Now, a new study published in the June issue of Immunity provides evidence that bacterial infections induce a kind of self-recognition that may contribute to some autoimmune diseases such as multiple sclerosis (MS) and Guillain-Barre syndrome (GBS).

There is evidence that the development of certain autoimmune diseases may be associated with a bacterial or viral infection that stimulates production of antibodies and immune cells called T cells, which are targeted against bacterial proteins that closely resemble “self” proteins, leading to crossreactivity with healthy tissues. Dr. Gennaro De Libero from University Hospital in Basel, Switzerland, and colleagues identified a different mechanism where bacterial infections promote activation of T cells that recognize molecules called glycosphingolipids (GSL) that are present in bacteria and humans. The researchers show that infection with some bacteria or even just exposure to pieces of the outer wall of the bacteria results in an increase in “self” GSL synthesis by cells that promote the immune response and subsequent stimulation of autoreactive GSL-specific T cells.

“Collectively, these findings suggest that recognition of self by infection is an important mechanism leading to autoreactive T cell activation and, possibly, participates in the pathogenesis of some autoimmune diseases, such as MS and GBS, in which the anti-GSL T cell response may be important,” writes Dr. De Libero. The authors suggest that although the autoreactive T cells may play a useful role in promoting the immune response to infection, in the absence of infection the GSL autoreactive T cells might seek out the abundant “self” GSLs that can be found in the nervous system, resulting in degradation of brain and nerve tissue as is seen in patients with MS and GBS.