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In Vivo Infection with Leishmania amazonensis to Evaluate Parasite Virulence in Mice
Published on: February 20, 2020
Factors influencing Leishmania major infection in IL-4-deficient BALB/c mice
1Imperial College London, Faculty of Medicine, Division of Investigative Science, Department of Immunology, London, UK. p.kropf@imperial.ac.uk
Abstract:
The outcome of Leishmania major infection in IL-4-deficient BALB/c mice has been a controversial subject. We have shown that IL-4-deficient BALB/c mice infected with Leishmania major developed progressive lesions and could not contain the replication of the parasites, whereas other studies have reported that IL-4-deficient mice were able to resist infection. Therefore, we examined different factors that can influence the course of Leishmania major infection. We tested different lines of IL-4-deficient BALB/c mice and show that the reported differences in the outcome of infection were not due to the different genetic origin of the embryonic stem cells used to disrupt the IL-4 gene. In addition, we infected IL-4-deficient mice with different isolates of L. major parasites and show that none of the parasite strains tested were cleared, although some of them caused milder pathology. Interestingly, this milder pathology was paralleled by a reduced arginase activity of the parasites. We also tested the influence of age on the course of Leishmania major infection in IL-4-deficient BALB/c mice and show that older mice express a transient resistance. Thus, we conclude that differences in the age of the mice and in the arginase activity of the different isolates of parasites are factors that can influence the non-healing phenotype of IL-4-/- BALB/c mice.
Insights
Investigating Leishmania major infection in IL-4-deficient mice revealed that parasite arginase activity and host age influence disease progression. Older mice showed transient resistance, while parasite strain impacted lesion severity.
Area of Science:
- Immunology
- Parasitology
- Genetics
Background:
- The outcome of Leishmania major infection in IL-4-deficient BALB/c mice is debated, with conflicting reports on resistance versus progressive disease.
- Previous studies reported differing results, necessitating an investigation into factors influencing Leishmania major infection in these mice.
Purpose of the Study:
- To identify factors contributing to the variable outcomes of Leishmania major infection in IL-4-deficient BALB/c mice.
- To resolve discrepancies in the literature regarding the role of IL-4 in Leishmania major infection control.
Main Methods:
- Tested different lines of IL-4-deficient BALB/c mice to rule out genetic background differences.
- Infected mice with various Leishmania major isolates to assess parasite strain impact.
- Evaluated the influence of host age on infection course.
- Measured arginase activity in parasites.
Main Results:
- Differences in infection outcomes were not attributable to the genetic origin of embryonic stem cells used for IL-4 gene disruption.
- No Leishmania major isolates were cleared, though some caused milder pathology correlated with reduced parasite arginase activity.
- Older IL-4-deficient mice exhibited transient resistance to infection.
Conclusions:
- Host age and parasite arginase activity are key factors influencing the non-healing phenotype in IL-4-deficient BALB/c mice.
- These factors help explain the controversial outcomes reported in previous studies of Leishmania major infection.
