The role of epithelial cells in mucosal inflammation in the zebrafish gut and gills

Mucosal barriers of the intestine and the lung offer the first line of protection in the host defense mechanisms against ingested and inhaled antigens. While long considered innocent bystanders simply forming a physical barrier, it is becoming increasingly evident that mucosal epithelial cells play a crucial role in maintaining immune homeostasis and mediating inflammation.

Initially we have found that a single exposure to a diet rich in cholesterol results in the accumulation of myeloid cells in the intestine in both zebrafish and mice. Pharmacological and genetic interventions demonstrated that cholesterol induces inflammasome activation in intestinal epithelial cells which in the longer-term leads to impaired intestinal motility. This model reveals a novel route by which dietary cholesterol can initiate intestinal inflammation.

To test whether similar processes could take place in the epithelium of the airways, we performed similar studies in the zebrafish gills, which is a non ciliated but otherwise equivalent epithelium to that of mammals. Adult zebrafish were exposed to cigarette smoke and we found that inflammatory cytokine production and myeloid cells were affected. We are currently studying the involvement of epithelium in the activation of pathways leading to this observation. Together, our models of mucosal inflammation illustrate the power of the zebrafish system to study pathophysiological responses induced within epithelial cells in a whole organism.