Brussels, 06 Feb 2006
A team from the University of Flanders in Belgium, working with colleagues from the University of Ghent, has discovered an important pathway set in motion by animals, including humans, when attacked by bacteria. The discovery sheds light on the way that bacteria is dealt with by the body, and could generate novel approaches for treating bacterial infections.
We know that bacteria can cause infection, but it is difficult for bacteria to even enter the human body, and systems work efficiently within the body to render bacteria harmless. However, if the bacteria are aggressive enough, our defences slow enough and perhaps our health poor enough, then we may become susceptible to infection.
In a normal body, the immune system detects and deals with bacteria by binding a receptor known as TLR4 to a bacterial wall component known as LPS. This starts a process of reactions causing a localised inflammation, which is what eliminates the bacteria.
If too much inflammation is produced, it is possible to go into a lethal shock. The team investigated a specific type of mouse (known as SPRET/Ei) that is resistant to LPS, and therefore resistant to LPS-induced shock.
In the experiment, the researchers gave the mice large doses of LPS to mimic a bacterial infection. This should have caused a great deal of inflammation, and the death of the mice, but they survived. The team suspected that the reason the mouse survived was due to a lack of type-1 interferons, which are part of the chain to generate an inflammation and rid the body of infection.
To test this, the team administered these type-1 interferons to the mouse, and then re-administered the LPS. This time, the mouse was susceptible to LPS, and developed inflammation. This shows that the type 1 interferons are an essential pathway in producing inflammation, and so an essential part of the body's chain of defences.
To test this, the researchers introduced the interferon-free mice to the listeria bacteria. Listeria is known to use an unusual pathway for attack, which involves the interferons. The mice were resistant to the listeria, as they expected, confirming that the resistance to LPS was due to an absence of interferons.
The pathways explored in this research may be implicated in other inflammation diseases, such as arthritis. Researcher Tina Mahieu explained: 'We didn't test this, as the experiment was specific for sepsis, so we really don't know. We found a molecule which could be important in other diseases, but we cannot broaden this out.'
For further information, please contact:
Dr Ann Van Gysel,