illustration by Leif Parsons

A Thermostat for Mucus

Our guts are constantly exposed to bacteria, some helpful, some harmful. If gut defenses aren’t strong when unfriendly bacteria attack, the pathogens can lead to increased susceptibility to diseases such as colon cancer and type 2 diabetes. Fortunately, humans and other animals have a thin lining of intestinal mucus that helps keep the bad guys at bay. Recently, three scientists—Richard Flavell, an HHMI investigator at Yale University, Eran Elinav at the Wiezmann Institute of Science, and Brett Finlay at the University of British Columbia—collaborated to show that this entire defense system depends on a protein complex called the NLRP6 inflammasome.

Inflammasomes are collections of proteins responsible for turning on immune responses that result in inflammation. In mice engineered to lack the NLRP6 inflammasome, no intestinal mucus shield was produced. Without that layer, the team reported on February 27, 2014, in Cell, bacteria began to attack the lining of the mouse gut, causing infection.

The scientists believe that the NLRP6 inflammasome acts as a thermostat that opens and closes the mucus faucet. The protein complex senses the amount of mucus needed and tells mucus-producing cells how much of the antimicrobial liquid to make. In mice without the NLRP6 inflammasome, the faucet stays closed and there is no mucus shield. This finding is surprising, Flavell explains, because “it was thought that the mucus layer was maintained in a constitutive fashion—in other words, it was essentially present at all times.”

They next plan to test whether the inflammasome-mucus system works the same way in humans and to figure out how to “dial up” the protective shield.

Scientist Profile

Investigator
Yale University
Immunology, Molecular Biology