Organoids as tools to investigate gastrointestinal nematode development and host interactions

Abstract

Gastrointestinal nematodes are a diverse class of pathogens that colonise a quarter of the world's human population and nearly all grazing livestock. These macroparasites establish, and some migrate, within host gastrointestinal niches during their life cycles and release molecules that condition the host mucosa to enable chronic infections. Understanding how helminths do this, and defining the molecules and mechanisms involved in host modulation, holds promise for novel strategies of anthelmintics and vaccines, as well as new knowledge of immune regulation and tissue repair. Yet the size and complexity of these multicellular parasites, coupled with the reliance on hosts to maintain their life cycles, present obstacles to interrogate how they interact with the gastric and intestinal epithelium, stroma and immune cells during infection, and also to develop protocols to genetically modify these parasites. Gastrointestinal organoids have transformed research on gastric and gut physiology during homeostasis and disease, including investigations on host-pathogen interactions with viruses, bacteria, protozoa and more recently, parasitic nematodes. Here we outline applications and important considerations for the best use of organoids to study gastrointestinal nematode development and interactions with their hosts. The careful use of different organoid culture configurations in order to achieve a closer replication of the in vivo infection context will lead not only to new knowledge on gastrointestinal nematode infection biology, but also towards the replication of their life cycles in vitro, and the development of valuable experimental tools such as genetically modified parasites.

Keywords: gastric epithelium; gastrointestinal nematodes; host-parasite interactions; immunomodulation; intestinal epithelium; nematode life cycles; organoid.

Figure 1

Comparison of sizes of examples of microorganisms that have been co-cultured with GI organoids with those of different life stages of the GI nematode Trichuris muris alongside a GI organoid. Values refer to the approximate diameter or length of each organism, images not to scale. Created with BioRender.com.