Coexisting with our bacteria

Our guts contain ten times more microbial cells than human cells. Why don’t our immune systems attack all these invaders? The answer may be that the bacteria don’t let us.

To be clear, it’s a very good thing that our immune systems don’t attack most of our gut flora. Many of these hitchhiking guests are extremely beneficial, helping us digest our food, providing nutrients and preventing more lethal invaders from finding living space. Still, even good bacteria are not human cells, and should be recognized as such and cleared by our immune systems. According to Sarkis Mazmanian and his colleagues from Caltech, the University of Chicago and UCLA, the reason this doesn’t happen is that bacteria can convince our immune systems that they are us.

The researchers found that rather than hiding from our immune systems in the lumen or center of our guts, as was previously thought, bacteria burrow deep into the mucosal surface of the colon. There, they activate a group of regulatory T (Treg) cells whose job it is to shut down our immune response. Ordinarily, Treg cells prevent our immune systems from attacking our own bodies. Without them, we suffer from such autoimmune diseases as arthritis, type 1 diabetes and lupus. In this case, the bacteria are tricking our immune system, by way of the Treg cells, into thinking that they are us. And for all practical purposes, perhaps they are us. Mazmanian suggests that we revise our concept of ‘self’ to include the trillions of microbes that have been part of us for our entire lives.

Caption: The image depicts symbiotic microbes in the process of colonizing the mucosal surface of the mouse colon. Yellow cells are Escherichia coli; red cells are Bacteroides fragilis. Intestinal tissues are labeled in green with blue nuclei.

Credit: S. Melanie Lee/Caltech.