Development of adult Dirofilaria immitis worms in the Rag2/Il-2rγ-/- mouse model

Abstract

Dirofilaria immitis is the causative agent for one of the major parasitic infections in dogs. It is currently not possible to reliably diagnose the infection before the development of fertile adult female worms and the presence of microfilariae which takes six to 7 months. However, at this point adult worms already reside in the pulmonary arteries and can cause significant damage. Novel in vivo models may facilitate the development of new diagnostic tools and improve treatment options for both the early and late stages of D. immitis infections. In this paper, we aimed to increase the capabilities of recently published mouse models in which severely immune-deficient mice were shown to be susceptible to D. immitis. Our data shows that D. immitis may grow into fully developed mature male and female worms in C57BL/6 Rag2/Il-2rγ^-/- mice with comparable growth rates to the natural canine host. The adult worms of D. immitis were shown to migrate into body cavities as well as the heart in this model. However, the presence of adult worms inside the heart of infected mice led to the development of caval syndrome in 36% of infected mice after five to 6 months. Overall, the current study complements recently published efforts to establish a D. immitis mouse model by extending the development of D. immitis into mature adult stages and will facilitate further preclinical research.