Immune control of parasitic infection: Defining the role of gel-forming mucins in protection against gastrointestinal nematodes

Infection by gastrointestinal parasites (GI) is one of the most common types of parasitic infection in man and animals worldwide. Despite a considerable increase in our understanding of the immunoregulatory mechanisms that govern the adaptive and innate immune responses to GI parasites, progress in defining the mechanisms of protection has been slow. It is becoming clear that to remove such large multicellular pathogens from the GI tract largely revolves around the capacity of host molecules and cells to directly affect the normal metabolic activity of the parasites reducing their fitness, or indirectly alter the niche in which the parasites live making it unfavourable for parasite survival. The net result is that parasites become damaged, are not often killed by the host response but are unable to reproduce optimally and are ultimately expelled out of the host during normal intestinal transit.

Type 2 cytokine responses control a variety of cellular changes in the intestinal epithelia associated with host protection against GI nematodes. One important feature is goblet cell hyperplasia. Despite the fact that the major secreted factors from goblet cells are the gel-forming mucins a clear role for these molecules in mucosal protection against GI nematodes has only recently been identified in our laboratories. We have identified a critical role for mucins in protective immunity to the GI nematode, Trichuris muris. We hypothesise that gel-forming mucins are a major effector mechanism involved in protection against intestinal nematodes. The goals of this project are to define how gel-forming mediate protection against Trichuris muris and investigate its protective function against other intestinal nematodes.

This project will provide the student with a comprehensive training in a broad range of biochemical, immunological, proteomic, in vitro and in vivo approaches; these will include gel chromatographic, electrophoretic and centrifugal separations, tandem mass spectrometry, cell culture, immunoassay and mouse models.