The Role of the Intestinal Epithelium in the "Weep and Sweep" Response during Gastro-Intestinal Helminth Infections.

Abstract

Simple SummaryThe immune system actively combats intruders such as bacteria, viruses, fungi, and protozoan and metazoan parasites using leukocytes. During an infection white blood cells are activated to internalize bacteria or viruses and release a number of molecules to kill pathogens. Unfortunately, those mechanisms are ineffective against larger intruders like helminths, which are too large to be killed by a single immune cell. To eliminate gastro-intestinal helminths an integrated response involving the nervous, endocrine, and immune systems are used to expel the parasites. This is achieved through increased gut hydration and muscle contractions which detach worms from the gut and lead to release outside the body in a “weep and sweep” response. Epithelial cells of the intestine are significant players in this process, being responsible for detecting the presence of helminths in the gut and participating in the regulation of parasite expulsion. This paper describes the role of the gut epithelium in detecting and eliminating helminths from the intestine.Helminths are metazoan parasites infecting around 1.5 billion people all over the world. During coevolution with hosts, worms have developed numerous ways to trick and evade the host immune response, and because of their size, they cannot be internalized and killed by immune cells in the same way as bacteria or viruses. During infection, a substantial Th2 component to the immune response is evoked which helps restrain Th1-mediated tissue damage. Although an enhanced Th2 response is often not enough to kill the parasite and terminate an infection in itself, when tightly coordinated with the nervous, endocrine, and motor systems it can dislodge parasites from tissues and expel them from the gut. A significant role in this “weep and seep” response is attributed to intestinal epithelial cells (IEC). This review highlights the role of various IEC lineages (enterocytes, tuft cells, Paneth cells, microfold cells, goblet cells, and intestine stem cells) during the course of helminth infections and summarizes their roles in regulating gut architecture and permeability, and muscle contractions and interactions with the immune and nervous system.