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 as a model for leishmaniasis. We have particularly emphasized the non-genetic factors that influence experiments and focused on strategies to improve translational value of studies on leishmaniasis using mouse models.

• Klíčová slova
• experimental analysis, experimental conditions, human leishmaniasis, influencing factor, mouse model, reproducibility of data, translation,
• MeSH
• Leishmania * imunologie   MeSH
• leishmanióza * parazitologie   imunologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech * MeSH
• myši MeSH
• reprodukovatelnost výsledků MeSH
• translační biomedicínský výzkum * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Phlebotomus perniciosus (Diptera: Phlebotominae) is a medically and veterinary important insect vector. It transmits the unicellular parasite Leishmania infantum that multiplies intracellularly in macrophages causing life-threatening visceral diseases. Leishmania establishment in the vertebrate host is substantially influenced by immunomodulatory properties of vector saliva that are obligatorily co-injected into the feeding site. The repertoire of P. perniciosus salivary molecules has already been revealed and, subsequently, several salivary proteins have been expressed. However, their immunogenic properties have never been studied. In our study, we tested three P. perniciosus recombinant salivary proteins-an apyrase rSP01 and yellow-related proteins rSP03 and rSP03B-and showed their anti-inflammatory nature on the murine bone-marrow derived macrophages. Even in the presence of pro-inflammatory stimuli (IFN-γ and bacterial lipopolysaccharide, LPS), all three recombinant proteins inhibited nitric oxide production. Moreover, rSP03 seems to have a very strong anti-inflammatory effect since it enhanced arginase activity, increased the production of IL-10, and inhibited the production of TNF-α even in macrophages stimulated with IFN-γ and LPS. These results suggest that P. perniciosus apyrase and yellow-related proteins may serve as enhancing factors in sand fly saliva, facilitating the development of Leishmania infection along with their anti-haemostatic properties. Additionally, rSP03 and rSP03B did not elicit the delayed-type hypersensitivity response in mice pre-exposed to P. perniciosus bites (measured as visible skin reaction). The results of our study may help to understand the potential function of recombinant's native counterparts and their role in Leishmania transmission and establishment within the host.

• Klíčová slova
• Phlebotomus, apyrase, immunogenicity, macrophage polarization, sand fly saliva, yellow-related proteins,
• MeSH
• antiflogistika MeSH
• fenotyp MeSH
• makrofágy MeSH
• myši MeSH
• Phlebotomus * MeSH
• psi MeSH
• rekombinantní proteiny MeSH
• slinné proteiny a peptidy MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antiflogistika MeSH
• rekombinantní proteiny MeSH
• slinné proteiny a peptidy MeSH