“Trillions of friendly bacteria inhabit our guts, and we want them there, but they have to be kept at arm's length.” Hooper has been investigating the relationship between the bacteria that live on or in other organisms—known collectively as the microbiota—and host tissue since 1996. Her interest in the DMZ dates to 2008, when she read a study describing this barrier in the mouse colon, or large intestine. "We started to wonder whether there were components of the immune system that were responsible for patrolling that barrier," Hooper says. Working with her colleagues at the University of Texas Southwestern Medical Center at Dallas, Hooper looked at mice lacking MyD88, a gene that encodes a signaling molecule that functions downstream of toll-like receptors. These receptors can sense bacteria and turn on the body's innate immune system. This year’s Nobel Prize in Physiology or Medicine was given partly in recognition of the discovery of toll-like receptors and their role in innate immunity. Mice missing MyD88 show 100 times more bacteria on the intestinal lining than do normal controls, the study found. The researchers saw the same thing in mice missing MyD88 only in epithelial cells, which line the surface of the intestine.
Hooper knew from previous work that MyD88 can turn on production of antibacterial proteins. To test if that was happening here, she looked at whether the presence of the DMZ correlated with the expression of MyD88 and an antibacterial protein called RegIIIγ She found that the DMZ stays intact only when both MyD88 and RegIIIγare fully expressed. The findings suggest that toll-like receptors sense the presence of the bacteria and then use MyD88 to alert the rest of the cell. MyD88 then spurs the production of RegIIIγ which kills the invading bacteria. "It's like a burglar alarm that senses your home is being invaded and radios the police," Hooper says. "The toll-like receptor is the alarm and RegIIIγis the police." It's likely that the gut has lots of alarm bells that work against different types of bacteria. RegIIIγonly kills Gram-positive bacteria—those that turn blue or purple when exposed to a Gram stain. About half of the bacteria in the gut are Gram-negative. "How do we keep our intestinal surfaces clear of Gram-negative bacteria?" Hooper asks. "One might predict that there are antibacterial proteins that can kill Gram-negatives that are also regulated in a similar manner. And so we’re searching for those."
RegIIIγis part of the innate immune response, but she also predicts that adaptive immune mechanisms also help keep gut bacteria at bay. Hooper is not only interested in how the microbiota interacts with its host, but how it interacts with viruses, such as polio, that live in the gut. In the same issue of Science, Hooper and senior author Julie Pfeiffer reported that mice treated with antibiotics are less susceptible to infection by poliovirus than are animals whose microbiota are left intact. Their collaborative work suggests that these viruses have evolved to exploit their bacterial neighbors to become more powerful.
Editorial Comment VetScite (MCH):
Even in the original article (Science 14 October 2011: Vol. 334 no. 6053 pp. 255-258 DOI: 10.1126/science.1209791) "The Antibacterial Lectin RegIIIγ Promotes the Spatial Segregation of Microbiota and Host in the Intestine", by Shipra Vaishnava et al., which is included in our recent News collection (Demilitarized zone' keeps gut bacteria where they belong), the authors quote the amount of microorganisms as "100 trillion bacteria", which is awkward in a scientific publication. The awkwardness is particularly apparent when looking at the vernacular "trillion", which means different things for different environments. As explained in Wikipedia, there are two interpretations of the quantity, according to a "long" and "short" scale: "Long scale ... refers to a system of large-number names in which every new term greater than million is 1,000,000 times the previous term: billion means a million millions (10e12), trillionmeans a million billions (10e18), and so on. Short scale ... refers to a system of large-number names in which every new term greater than million is 1,000 times the previous term: billion means a thousand millions (10e9), trillion means a thousand billions (10e12), and so on... For most of the 19th and 20th centuries, the United Kingdom uniformly used the long scale, while the United States of America used the short scale" Though most readers will only perceive "there is a lot of them", I think authors should stick to the scientific notation and refrain from using terms more appropriate in the financial lingo.
Howard Hughes Medical Institute
December 13, 2011
Original web page at Howard Hughes Medical Institute
