Defining the early stages of intestinal colonisation by whipworms.
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Authors
Goulding, David
Rodgers, Faye H
Gillis, J Andrew
Cormie, Claire
Bancroft, Allison J
Lotkowska, Magda E
Scott, Paul
Redshaw, Nicholas
McCarthy, Catherine
Brandt, Cordelia
Sharpe, Catherine
Ridley, Caroline
Moya, Judit Gali
Starborg, Tobias
Holroyd, Nancy
Sanders, Mandy
Publication Date
2022-04-01Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Springer Science and Business Media LLC
Volume
13
Issue
1
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Duque-Correa, M. A., Goulding, D., Rodgers, F. H., Gillis, J. A., Cormie, C., Rawlinson, K. A., Bancroft, A. J., et al. (2022). Defining the early stages of intestinal colonisation by whipworms.. Nat Commun, 13 (1) https://doi.org/10.1038/s41467-022-29334-0
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.
Keywords
Intestines, Intestinal Mucosa, Animals, Mammals, Mice, Helminths, Trichuris, Trichuriasis
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)
Identifiers
35365634, PMC8976045
External DOI: https://doi.org/10.1038/s41467-022-29334-0
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336816
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