Improving reproducibility and translational potential of mouse models: lessons from studying leishmaniasis

Mahmoud Nateghi-Rostami ¹ Marie Lipoldova ² Yahya Sohrabi ^3*

• ¹ Department of Parasitology, Pasteur Institute of Iran, Tehran, Alborz, Iran
• ² Department of Medical Genetics, Third Faculty of Medicine, Charles University, Prague, Prague, Czechia
• ³ Molecullare and Cellular Immunology, Department of Cardiology I, University Hospital Münster, Münster, Prague, Germany

Leishmaniasis is a complex disease caused by protozoan parasites of the genus Leishmania, which are transmitted by phlebotomine sand flies. The clinical manifestations of leishmaniasis are diverse, ranging from self-healing cutaneous lesions to fatal systemic disease. Mouse models are instrumental in advancing our understanding of the immune system against infections, yet their limitations in translating findings to humans are increasingly highlighted. The success rate of translating data from mice to humans remains low, largely due to the complexity of diseases and the numerous factors that influence the disease outcomes. Therefore, for the effective translation of data from murine models of leishmaniasis, it is essential to align experimental conditions with those relevant to human infection. Factors such as parasite characteristics, vector-derived components, host status, and environmental conditions must be carefully considered and adapted to enhance the translational relevance of mouse data. These parameters are potentially modifiable and should be carefully integrated into the design and interpretation of experimental procedures in Leishmania studies. In the current paper, we review the challenges and perspective of using mouse model as a model for leishmaniasis. We have particularly emphasized the non-genetic factors that influence experiments and on strategies to improve translational value of studies on leishmaniasis using mouse models.