Use of In Vivo Imaging System Technology in Leishmania major BALB/c Mouse Ear Infection Studies

Alicia Cawlfield1, Brian Vesely1, Franklyn Ngundam1

  • 1Walter Reed Army Institute of Research, Silver Spring, MD.

Insights

Developing a new mouse model for cutaneous leishmaniasis (CL) infection in the ear dermis improves assessment of antileishmanial drug efficacy. This optimized model better mimics human disease for evaluating novel CL treatments.

Area of Science:

  • Parasitology and Tropical Diseases
  • Infectious Disease Modeling
  • Drug Discovery and Development

Background:

  • Current cutaneous leishmaniasis (CL) treatments face challenges including parasite resistance, toxicity, and impracticality.
  • Existing mouse models (BALB/c, Golden Syrian Hamster) with high Leishmania parasite loads lack disease similarity to human CL.
  • Sand fly saliva influences host response to Leishmania infection, a factor often overlooked in current models.

Purpose of the Study:

  • To develop and optimize an in vivo model for cutaneous leishmaniasis (CL) in the ear dermis of BALB/c mice.
  • To evaluate different infection methods, including parasites alone, sand fly bites, or salivary gland sonicate, for Leishmania major.
  • To establish a more relevant model for assessing the efficacy of novel antileishmanial drug compounds.

Main Methods:

  • BALB/c mice were infected with luciferase-expressing Leishmania major in the ear dermis.
  • Infection methods compared: parasites alone, parasites with bites from uninfected Phlebotomus duboscqi sand flies, or with sand fly salivary gland sonicate.
  • Parasite load was monitored via bioluminescent signal; dermal lesion development and Leishmania Donovan Units in liver and spleen were assessed.

Main Results:

  • A dose-response relationship was observed for bioluminescent signal, indicating parasite load.
  • Dermal lesion development and parasite burden in the liver and spleen showed clear responses to infection methods.
  • The optimized ear dermis infection model demonstrated sensitivity to infection parameters.

Conclusions:

  • The developed in vivo Leishmania major ear infection model offers a more suitable platform for evaluating antileishmanial drug efficacy.
  • This model addresses limitations of previous CL models by incorporating relevant infection dynamics.
  • Further optimization of this model can facilitate the discovery and development of effective treatments for cutaneous leishmaniasis.

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