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Defining the early stages of intestinal colonisation by whipworms.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Duque-Correa, María A  ORCID logo  https://orcid.org/0000-0002-0567-0412
Goulding, David 
Rodgers, Faye H 
Gillis, J Andrew 
Cormie, Claire 

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.

Description

Keywords

Animals, Helminths, Intestinal Mucosa, Intestines, Mammals, Mice, Trichuriasis, Trichuris

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

13

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (206194, Z10661/Z/18/Z, 088785/Z/09/Z)
National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/P001521/1)