Background: In a murine model of inflammatory bowel disease (IBD), treatment of colitis in IL-10 gene-deficient mice with the parasitic helminth Heligmosomoides polygyrus ameliorates colonic inflammation. The cellular and molecular mechanisms driving this therapeutic host response are being studied vigorously. One proposed mechanism is that H. polygyrus infection favors the outgrowth or suppression of certain bacteria, which in turn help modulate host immunity.
Methods: To quantify the effect of H. polygyrus infection on the composition of the gastrointestinal (GI) tract microbiota, we conducted two independent microbial ecology analyses of C57BL/6 mice. We obtained and analyzed 3,353 bacterial 16S rRNA encoding gene sequences from the ileum and cecum of infected and uninfected mice as well as incective H. polygyrus larvae at the outset of the second experiment and adult worms taken directly from the mouse duodenum at the end of the second experiment.
Results: We found that a significant shift in the abundance and relative distribution of bacterial species in the ileum of mice is associated with H. polygyrus infection. Members of the bacterial family Lactobacillaceae significantly increased in abundance in the ileum of infected mice reproducibly in two independent experiments despite having different microbiotas present at the outset of each experiment.
Conclusions: These data support the concept that helminth infection shifts the composition of intestinal bacteria. The clinical consequences of these shifts in intestinal flora are yet to be explored.
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http://dx.doi.org/10.1002/ibd.21299 | DOI Listing |
Sci Immunol
December 2024
Department of Immunobiology, Université de Lausanne, Epalinges, Switzerland.
The molecular mechanisms by which worm parasites evade host immunity are incompletely understood. In a mouse model of intestinal helminth infection using (), we show that helminthic glutamate dehydrogenase (heGDH) drives parasite chronicity by suppressing macrophage-mediated host defense. Combining RNA-seq, ChIP-seq, and targeted lipidomics, we identify prostaglandin E (PGE) as a major immune regulatory mechanism of heGDH.
View Article and Find Full Text PDFEMBO Rep
November 2024
Centre for Parasitology, School of Infection and Immunity, University of Glasgow, Glasgow, G12 8TA, UK.
The immunoregulatory cytokine TGF-β is pleiotropic due to the near-ubiquitous expression of the TGF-β receptors TβRI and TβRII on diverse cell types. The helminth parasite Heligmosomoides polygyrus has convergently evolved a family of TGF-β mimics (TGMs) that bind both these receptors through domains 1-3 of a 5-domain protein. One member of this family, TGM4, differs from TGF-β in acting in a cell-specific manner, failing to stimulate fibroblasts, but activating SMAD phosphorylation in macrophages.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Department of Medicine, University of Otago, 23A Mein St., Newtown, Wellington 6242, New Zealand.
Infecting humans with controlled doses of small intestinal helminths, such as human hookworm, is proposed as a therapy for the colonic inflammatory disease ulcerative colitis. Strengthening the colonic mucus barrier is a potential mechanism by which small intestinal helminths could treat ulcerative colitis. In this study, we compare C57BL/6 mice infected with the small intestinal helminth and uninfected controls to investigate changes in colonic mucus.
View Article and Find Full Text PDFElife
November 2024
Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
PLoS Negl Trop Dis
October 2024
Program in Molecular Medicine, UMASS Chan Medical School, Worcester, Massachusetts, United States of America.
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