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Updated: May 20, 2026
In Vivo Infection with Leishmania amazonensis to Evaluate Parasite Virulence in Mice
Published on: February 20, 2020
Leishmania major infection in humanized mice induces systemic infection and provokes a nonprotective human immune
Anja Kathrin Wege1, Christian Florian, Wolfgang Ernst
1Institute of Immunology, University of Regensburg, Regensburg, Bavaria, Germany.
Background:
Leishmania (L.) species are the causative agent of leishmaniasis. Due to the lack of efficient vaccine candidates, drug therapies are the only option to deal with cutaneous leishmaniasis. Unfortunately, chemotherapeutic interventions show high toxicity in addition to an increased risk of dissemination of drug-resistant parasites. An appropriate laboratory animal based model is still missing which allows testing of new drug strategies in the context of human immune cells in vivo.
Methodology/Principal Findings:
Humanized mice were infected subcutaneously with stationary phase promastigote L. major into the footpad. The human immune response against the pathogen and the parasite host interactions were analyzed. In addition we proved the versatility of this new model to conduct drug research studies by the inclusion of orally given Miltefosine. We show that inflammatory human macrophages get infected with Leishmania parasites at the site of infection. Furthermore, a Leishmania-specific human-derived T cell response is initiated. However, the human immune system is not able to prevent systemic infection. Thus, we treated the mice with Miltefosine to reduce the parasitic load. Notably, this chemotherapy resulted in a reduction of the parasite load in distinct organs. Comparable to some Miltefosine treated patients, humanized mice developed severe side effects, which are not detectable in the classical murine model of experimental leishmaniasis.
Conclusions/Significance:
This study describes for the first time L. major infection in humanized mice, characterizes the disease development, the induction of human adaptive and innate immune response including cytokine production and the efficiency of Miltefosine treatment in these animals. In summary, humanized mice might be beneficial for future preclinical chemotherapeutic studies in systemic (visceral) leishmaniasis allowing the investigation of human immune response, side effects of the drug due to cytokine production of activated humane immune cells and the efficiency of the treatment to eliminate also not replicating ("hiding") parasites.
Insights
A new humanized mouse model effectively mimics leishmaniasis, showing human immune responses and Miltefosine efficacy. This model reveals drug side effects and parasite load reduction, aiding future leishmaniasis drug development.
Area of Science:
- Immunology
- Parasitology
- Pharmacology
Background:
- Leishmania species cause leishmaniasis, a disease treated with toxic drugs due to a lack of vaccines.
- Current treatments for leishmaniasis face challenges with toxicity and drug resistance.
- An in vivo model using human immune cells is needed for effective drug testing.
Purpose of the Study:
- To establish and characterize a humanized mouse model for studying Leishmania major infection.
- To analyze the human immune response and parasite-host interactions in vivo.
- To evaluate the efficacy and side effects of Miltefosine treatment in this novel model.
Main Methods:
- Humanized mice were infected with Leishmania major.
- Human immune responses, including T cell activation and cytokine production, were analyzed.
- The efficacy of Miltefosine treatment was assessed by measuring parasite load and observing side effects.
Main Results:
- Humanized mice developed Leishmania infections with inflammatory macrophage involvement.
- A Leishmania-specific human T cell response was initiated, but systemic infection was not prevented.
- Miltefosine treatment reduced parasite load in organs and caused side effects similar to human patients.
Conclusions:
- This study presents the first characterization of Leishmania major infection in a humanized mouse model.
- The model allows for the study of human innate and adaptive immune responses to leishmaniasis.
- Humanized mice are a promising preclinical tool for evaluating leishmaniasis drug efficacy and toxicity.
