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.

The researchers include Gennaro De Libero, Hans-Jürgen Gober, Emmanuel Rossy, Sebastiano Sansano, Regine Landmann, and Lucia Mori of the University Hospital, Basel; Anthony P. Moran and Martina M. Prendergast of the National University of Ireland, Galway; Alexander Tonevitsky of the Institute for Genetics of Microorganisms, Moscow; Abdijapar Shamshiev (University Hospital, Basel) presently at Swiss Federal Institute of Technology Zurich; Olga Chelnokova of University Hospital, Basel and Institute for Genetics of Microorganisms, Moscow; Zurich Zaima Mazorra (University Hospital, Basel) presently at Center of Molecular Immunology, Havana; and Silvia Vendetti and Alessandra Sacchi of the Istituto "Lazzaro Spallanzani," Rome. This work was supported by the International Association for the Promotion of Cooperation with scientists from the New Independent States (NIS) of the Former Soviet Union (INTAS); the Swiss National Fund; the Human Frontier Science Program; the Swiss Multiple Sclerosis Society; the Italian Public Health Ministry; and by the Irish Health Research Board.

De Libero, G., Moran, A.P., Gober, H.-J., Rossy, E., Shamshiev, A., Chelnokova, o., Mazorra, Z., Vendetti, S., Sacchi, A., Prendergast, M.M., Sansano, S., Tonevitsky, A., Landmann, R., and Mori, L. (2005). Bacterial Infections Promote T Cell Recognition of Self-Glycolipids. DOI 10.1016/j.immuni.2005.04.013. Publishing in Immunity, Vol. 22, June, 2005, pages 763–772. http://www.immunity.com/

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