Senin, 02 Juli 2012

The battle in the body: Watch as an infection takes hold before it is beaten back by the immune system

The battle in the body: Watch as an infection takes hold before it is beaten back by the immune system

By Claire Bates

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It is one of nature's most fierce battles, in many cases a matter of life and death.

And now for the first time scientists have shown, in real-time, how a bacterial infection can spread - and how the immune system kicks in to fight it off.

Researchers infected a mouse with a light-emitting stomach bug and tracked to see where it took hold and how far it spread through the body before it was eventually killed off.

They discovered that the entire infection cycle took 12 days.

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Day 0 Day1

The mouse before the infection (left) and on day one (right) where the bacteria is mostly visible in the small intestine

Day 5 Day 6

On day four (left) the bacteria is only visible in the cecum part of the intestine, but the infection is just adapting to the mouse's body. By day six (right) it launches a full-scale attack and spreads to the rectum

The team from Imperial College London used a version of the bacteria 'Citrobacter rodentium', which they had genetically modified to produce light and tracked using state-of-the-art 3D scanning equipment

Each day they placed the mouse in the in vivo scanner - made up of a dark box with a sensitive bioluminescence camera at the top.

They charted the bacteria's course by analysing the tiny amounts of light that escaped from the animal. More light meant there was more bacteria in that area.

HOW THE INFECTION SPREAD

The scientists followed the mouse from just before it was infected on day 0 for 11 days. On day one post infection they detected the bacteria mainly in the small intestine.

From day two to four they found the number of bacterium in the gut increased, however it was becoming restricted to the part of the intestine known as the cecum.

On day five the pathogen was only seen in the 'lymphoid follicle' of the cecum - an area that usually removes bacteria from the system.

'We believe this is where the pathogen (bug) adapts to the in vivo (internal) environment of the host,' the scientists said.

But on day six the infection stepped up a gear and spreads from the cecum to the distal part of the rectum. By day eight the entire colon was heavily colonised by the bacteria.

However, on day nine the mouse's body mounted a counter-attack. The immune response started to clear the infection in reverse order - first from the colon and then from the cecum.

By day 12 the battle was over and no more Citrobacter rodentium is visible in sca ns. The mouse has effectively recovered from the infection.

day 8 day 9

By day eight (left) the colon is heavily infected but by day nine (right) the immune system responds

day 10 day 11

On day 10 (left) and day 11 (right) the infection starts to recede

Study leader Professor Frankel, said the technique was 'revolutionary' and would help scientists develop new strategies in fighting bacterial infections, which often become resistant to antibiotics.

He added: 'The infection of mice with Citrobacter rodentium is an excellent model to study infection with E. coli 0157 in humans.'

That particular strain of E coli is a severe and sometime fatal form of infectious gastroenteritis that is most dangerous to children and the elderly.

The team used the biological imaging centre at Imperial College's new MRC Centre for Molecular Bacteriology and Infection.







 





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