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Cambridge University Science Magazine

Hoffmann’s extensive research with fruit flies led him to discover that products of the Toll gene acted as sensors of pathogenic microorganisms. Former Nobel Prize winner Christiane Nüsslein-Volhard had previously shown that Toll was involved in embryonic development. Hoffmann demonstrated that Toll activation was also a vital step in immune system defence against pathogens.

Quite separately, Beutler had been searching for a receptor to bind lipopolysaccharide (LPS). LPS is a bacterial product that causes septic shock - a potentially life-threatening condition that involves overstimulation of the immune system. Beutler found similarities between a mutation in a gene present in LPS-resistant mice and the Toll gene that Hoffmann had been working with in fruit flies. Experiments confirmed that the Toll gene was indeed the elusive LPS receptor which, when bound to LPS, activates the signals that cause inflammation and, in extreme cases, septic shock. These findings were remarkable in that they suggested that mammals and fruit flies use similar molecules to activate their immune systems when faced with pathogenic microorganisms.

The third winner, Ralph Steinman, had previously discovered a new cell type, which he named the ‘dendritic cell’. He showed that dendritic cells stimulate T cells – immune cells that form immunologic “memories” of invading pathogens and play an important part in improving the adaptability of the immune system. This discovery of dendritic cells and their interaction with T cells thus shed light on the main mechanism by which the immune system decides to react towards pathogenic microorganisms.

These findings have paved the way for innovative methods for preventing and treating diseases. Examples include improved vaccines and attempts to incentivise the immune system to attack cancerous tumours. Furthermore, the findings have enhanced our understanding of how and why the immune system can attack our own tissues, renewing efforts to find new treatments for inflammatory diseases.

Written by Javier Azpiroz-Korban