The inner surfaces of our intestines are covered with bacteria. In fact most of our feces is composed of microbes (10 trillion organisms per gram). These microbes are very valuable to the health of our gastrointestinal tract. Certain bacteria in our intestines product vitamin D. These microbes also prevent the attachment and growth of bacteria that cause disease in our intestines. Even though these microbes are useful they are foreign to our bodies and scientists for ages have wondered why our bodies do not mount an immune response to these beneficial microbial passengers (commensals). Recent articles in Science Vol. 289, No. 5484, pp. 1483 and 1560) describe one means commensal bacteria may use to lower the immune response to their being in the intestine.
Previous investigators have demonstrated that cells lining the intestine can induce the immune system to respond to invading bacteria. These cells do this by allowing a master transcription factor NF-kB to induce the production of various factors that turn on the immune system. These factors are called TNF (tumor necrosis factor) and IL-8 (interleukin-8). To prevent this transcription factor from constantly turning on the immune system an inhibitor of NF-kB is constantly attached to the transcription factor. When a disease causing bacteria interacts with a cell lining the intestine the cell then eliminates the inhibitor of NF-kB so that it can initiate production of TNF and IL-8.
Andrew S. Neish, et. al. have found that commensal bacteria are able to prevent activation of the immune system by these cells lining the intestine. These commensal bacteria do this by preventing the elimination of the inhibitor of NF-kB. As a result, NF-kB is never able to turn on the production of TNF and IL-8. Without TNF and IL-8 no immune response and the commensal bacteria can live in happy harmony inside the intestine.
Bacteria that cause infections don’t appear to have this ability to prevent the elimination of the inhibitor of NF-kB and as a result an immune response will result. An interesting side note is that many of the drugs used to inhibit chronic inflammation of the intestines also prevent the elimination of the inhibitor of NF-kB. With this knowledge it might be possible to design drugs that could better inhibit inflammation of the intestine and help patients with chronic intestinal problems (Crohn’s disease, chronic colitis, etc.).