AUTOIMMUNE
May 3, 2011

Our Bacteria, Our Selves

The bacteria in our gut manage to evade an immune system designed to attack them. How?

Our immune system serves as a bodily security system. Its job is to track down and eliminate organisms that invade the body, chiefly bacteria. At the same time, the human gut normally contains about a thousand species of bacteria and as many as one trillion total bacterial cells. Many of these bacteria are beneficial and normally none cause us any harm.

So how is it that our normal intestinal flora manage to evade the immune system and live harmoniously within us?

Polysaccharide A acts as a kind of molecular ID card. It defines the bacteria as self and not non-self, friend and not foe.

Researchers at Caltech (the California Institute of Technology) have found an answer to this question. Working with mice, they have found how one bacterium, Bacteroides fragilis, manages this feat. They also suggest that we might want to broaden our view of what our "self " truly includes.

These Bacteroides fragilis bacteria live deep in the colon of humans and mice. They contain a molecule called polysaccharide A on their cell surface. This molecule communicates with the immune system and shuts down the process that normally would attack these bacteria. Polysaccharide A acts as a kind of molecular ID card. It defines the bacteria as self and not non-self, friend and not foe.

B. fragilis contains eight different polysaccharides (large sugar molecules) on its surface, one of them being polysaccharide A. These cover the bacterium much like the hair on a kiwi fruit. Normally, foreign polysaccharides like these ramp up the immune system, causing production of large numbers of antibodies in an attempt to eliminate the bacteria. But polysaccharide A instead dampens the overall immune activity in the area of the colon where B. fragilis lives.

The presence of polysaccharide A increases the activity of T-regulatory (treg) cells, which in turn causes suppression of a pro-inflammatory immune cell called Th17. By shutting down local Th17 cells, B. fragilis is spared from immune attack and is left free to colonize the colon and keep it healthy.

The researchers have already used the bacterium to successfully treat certain mice with inflammatory bowel disease.

When the researchers used mutant B. fragilis that lacked polysaccharide A, the bacteria were attacked by the mouse immune system and expelled from the colon. This also occurred when the treg cell receptor for polysaccharide A was eliminated or when treg cells themselves were absent. In all these cases, the bacterium was no longer recognized as self and was seen as an invader.

This is the first case where a normal gut bacterium has been shown to produce a specific molecule that moderates the immune system. It's possible that other bacteria also produce such molecules.

Human autoimmune diseases occur when the immune system begins attacking normal human tissue. Researcher Sarkis K. Mazmanian, an assistant professor of biology, suspects that genetic mutations in these pathways could be responsible for certain types of immune disorders, including inflammatory bowel disease. As he put it in a Caltech press release, "The question is, do patients get sick because they are rejecting bacteria they shouldn't reject?" Polysaccharide A or B. fragilis itself might prove useful in treating these conditions, and in fact, the researchers have already used the bacterium to successfully treat certain mice with inflammatory bowel disease.

On a philosophical level, the researchers suggest that people might want to take a wider self-view that includes our vast number of bacterial roommates. After all, the immune system recognizes them as part of our self. Maybe we should, too.

After a week of taking antibiotics, people usually say that they don't quite feel like themselves. Maybe that's because they aren't themselves; they're missing their normal bacterial partners that the antibiotics have killed. Without them, they're just not complete.

An article on the research was published online by Science Express on April 21, 2011 and will also appear in a future edition of Science.

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