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

[Guest guest]

Public release date: 21-Jun-2005

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.

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The researchers include Gennaro De Libero, Hans-Jürgen Gober, Emmanuel

Rossy, Sebastiano Sansano, Regine Landmann, and Lucia Mori of the

University Hospital, Basel; P. Moran and a M. Prendergast

of the National University of Ireland, Galway; 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 ation 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/