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IL-4 dependent resistance to the tapeworm Mesocestoides corti (Cestoda) in mice
Jagveer Rawat1, John B Dixon, Andrew R Macintyre
1Department of Veterinary Pathology, University of Liverpool, L69 3BX, UK.
Abstract:
Three-week Mesocestoides corti infections of C57BL/6 mice showed significantly raised parasite counts in animals with a targeted knockout of the IL-4 gene. By contrast, antibody neutralization of IL-5 and inhibition of eosinophilia had no effect on parasite numbers. In SV/129 mice, knockout of the interferon gamma receptor and inducible nitric oxide synthase genes had no significant effect on parasite counts. In IL-4(-/-)mice the dominant IgG1 antibody response was dramatically reduced, with a concomitant increase in IgG2a/b responses and a partial twofold reduction in IgM and IgE responses. We conclude that murine resistance to M. corti is dependent on IL-4, but occurs independently of IL-5 and eosinophils. This provides the first direct evidence for IL-4 mediated immunity of mice to infection with a tissue-dwelling platyhelminth.
Insights
Murine resistance to Mesocestoides corti infection depends on interleukin-4 (IL-4), but not on interleukin-5 (IL-5) or eosinophils. This study highlights IL-4
Area of Science:
- Immunology
- Parasitology
- Helminthology
Background:
- Interleukin-4 (IL-4) is a cytokine crucial for regulating immune responses.
- The role of IL-4 in immunity against tissue-dwelling helminths, such as Mesocestoides corti, requires further elucidation.
- Understanding host-parasite interactions is vital for developing effective treatments.
Purpose of the Study:
- To investigate the role of IL-4 in murine resistance to Mesocestoides corti infection.
- To determine whether IL-5 and eosinophils contribute to resistance against this parasite.
- To elucidate the antibody response profile in the absence of IL-4.
Main Methods:
- Utilizing knockout mouse models (IL-4(-/-), interferon gamma receptor knockout, inducible nitric oxide synthase knockout).
- Infecting mice with Mesocestoides corti larvae.
- Quantifying parasite burden.
- Analyzing host antibody responses (IgG1, IgG2a/b, IgM, IgE) via ELISA or similar techniques.
- Administering antibodies to neutralize IL-5 and inhibit eosinophilia.
Main Results:
- Significantly higher parasite counts were observed in IL-4 gene knockout mice compared to controls.
- Neutralization of IL-5 and inhibition of eosinophilia did not affect parasite numbers.
- In SV/129 mice, knockout of interferon gamma receptor and inducible nitric oxide synthase genes showed no significant impact on parasite counts.
- IL-4 deficiency led to a reduced IgG1 response, increased IgG2a/b, and decreased IgM and IgE levels.
Conclusions:
- Murine resistance to Mesocestoides corti is critically dependent on IL-4.
- IL-4 mediated immunity against this tissue-dwelling platyhelminth occurs independently of IL-5 and eosinophils.
- This study provides the first direct evidence for IL-4's role in conferring resistance to helminth infections in mice.
