Article Text

PDF
GI highlights from the literature
  1. Mairi H McLean, Education editor

Statistics from Altmetric.com

Basic science

The goblet cell hits the spotlight: a key player in host-microbial interaction

▸ Wlodarska M, Thaiss CA, Nowarski R, et al. NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion. Cell 2014;156:1045–59.

The inflammasome is a cytosolic complex of proteins that hold a key role in both homeostasis and disease development. There are several proteins in the complex, such as NLR proteins, ASC and caspase-1. NLRP6 is highly expressed in colonic epithelial cells and is important in epithelial restoration and repair, response to infection and regulation of microbial luminal communities. In fact, nlrp6−/− mice are associated with colitogenic microbiota in the crypt base, but the mechanisms behind this are not understood. In this study, nlrp6−/− mice were less able to clear infection by Citrobacter rodentium, although they did display the same robust mucosal immune response as wild-type mice, including expression of inflammasome-related cytokines IL-1β and IL-18, suggesting an underlying non-immune-mediated mechanism. In situ hybridisation revealed that nlrp6 expression is focused on the apical surface of goblet cells within the epithelial barrier. These specialised cells secrete muc2 mucin that acts as a physical barrier ultimately preventing luminal bacterial interaction with the mucosal surface, and translocation of bacteria into the host. Further work using a series of genetically altered mice revealed that deficiency in the NLRP6 inflammasome was associated with a reduced mucus layer due to the inability of goblet cell vesicles to bind to the apical basement membrane and release their contents. Mechanistically, this was due to a lack of inflammasome-regulated autophagy in these cells. This paper reports a novel key regulatory component of host-microbial interaction at the gastrointestinal interface. This inflammasome-mediated mechanism could increase understanding of disease pathogenesis and may identify new therapeutic targets for GI disease.

PGE2: the missing link between cirrhosis and infection risk

▸ O’Brien AJ, Fullerton JN, Massey KA, et al. Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E2. …

View Full Text

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.