Defining the early stages of intestinal colonisation by whipworms

María A Duque-Correa, David Goulding, Faye H Rodgers, J Andrew Gillis, Claire Cormie, Kate A Rawlinson, Allison J Bancroft, Hayley M Bennett, Magda E Lotkowska, Adam J Reid, Anneliese O Speak, Paul Scott, Nicholas Redshaw, Charlotte Tolley, Catherine McCarthy, Cordelia Brandt, Catherine Sharpe, Caroline Ridley, Judit Gali Moya, Claudia M CarneiroTobias Starborg, Kelly S Hayes, Nancy Holroyd, Mandy Sanders, David J Thornton, Richard K Grencis, Matthew Berriman

Research output: Contribution to journalArticlepeer-review

Abstract

Whipworms are large metazoan parasites that inhabit multi-intracellular epithelial tunnels in the large intestine of their hosts, causing chronic disease in humans and other mammals. How first-stage larvae invade host epithelia and establish infection remains unclear. Here we investigate early infection events using both Trichuris muris infections of mice and murine caecaloids, the first in-vitro system for whipworm infection and organoid model for live helminths. We show that larvae degrade mucus layers to access epithelial cells. In early syncytial tunnels, larvae are completely intracellular, woven through multiple live dividing cells. Using single-cell RNA sequencing of infected mouse caecum, we reveal that progression of infection results in cell damage and an expansion of enterocytes expressing of Isg15, potentially instigating the host immune response to the whipworm and tissue repair. Our results unravel intestinal epithelium invasion by whipworms and reveal specific host-parasite interactions that allow the whipworm to establish its multi-intracellular niche.

Original languageEnglish
Pages (from-to)1725
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - 1 Apr 2022

Keywords

  • Animals
  • Helminths
  • Intestinal Mucosa
  • Intestines/parasitology
  • Mammals
  • Mice
  • Trichuriasis
  • Trichuris/physiology

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