Related Experiment Videos
IL-4-regulated enteropathy in an intestinal nematode infection
C E Lawrence1, J C Paterson, L M Higgins
1Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, GB. gvna11@udcf.gla.ac.uk
European Journal of Immunology
|October 1, 1998
Summary
Immune responses to intestinal nematodes involve T helper 2 (Th2) cells and interleukin-4 (IL-4). This study reveals IL-4, not IFN-gamma, drives intestinal pathology, and tumor necrosis factor (TNF) mediates this pathology, not parasite expulsion.
Area of Science:
- Immunology
- Parasitology
- Gastroenterology
Background:
- The link between intestinal pathology and parasite expulsion in helminth infections is unclear.
- Immune expulsion of nematodes is T cell-dependent, typically involving Th2 responses.
- Effector mechanisms of parasite expulsion and the role of cytokines in associated pathology require elucidation.
Purpose of the Study:
- To investigate the roles of specific cytokines, including IL-4, IFN-gamma, and TNF, in regulating intestinal pathology and parasite rejection.
- To clarify the cytokine-dependent mechanisms underlying immune-mediated expulsion of the nematode Trichinella spiralis.
- To determine the relationship between intestinal immunopathology and parasite clearance.
Main Methods:
- Utilized genetically modified mice lacking specific cytokine or cytokine receptor functions.
- Infected these mice with the nematode Trichinella spiralis.
- Assessed the development of intestinal pathology and the efficiency of parasite expulsion.
Main Results:
- Parasite expulsion was confirmed to be dependent on IL-4.
- Contrary to hypotheses, IL-4, not IFN-gamma, was found to regulate intestinal enteropathy.
- Mice lacking TNF receptors showed reduced pathology but still expelled parasites, indicating TNF's role in pathology, not expulsion.
Conclusions:
- IL-4 plays a dual role, mediating both parasite expulsion and intestinal pathology.
- TNF contributes to intestinal pathology in nematode infections, regulated by IL-4 and Th2 responses.
- Parasite clearance mechanisms are distinct from the gross environmental degradation caused by immune-mediated enteropathy.