Drastic Reduction of a Filarial Infection in Eosinophilic Interleukin-5 Transgenic Mice

Abstract

ABSTRACT In order to establish the role of eosinophils in destroying parasites, transgenic mice have been used in experimental helminthiases but not in filariasis. Litomosoides sigmodontis offers a good opportunity for this study because it is the only filarial species that completes its life cycle in mice. Its development was compared in transgenic CBA/Ca mice overexpressing interleukin-5 (IL-5) and in wild-type mice following subcutaneous inoculation of 40 infective larvae. An acceleration of larval growth was observed in the IL-5 transgenic mice. However, the recovery rate of adult worms was considerably reduced in these mice, as evidenced 2 months postinoculation (p.i.). The reduction occurs between days 10 and 30 p.i. in the coelomic cavities. As early as day 10, spherical aggregates of eosinophils and macrophages are seen attached on live developing larvae (always similarly localized on the worm) in both wild-type and transgenic mice. However, on day 60 p.i., granulomas were found in the transgenic mice only, probably because of the higher density of eosinophils. Furthermore, on day 30 p.i., young filariae are seen trapped in granulomas, some of them surrounded by Splendore-Hoeppli deposits, which illustrates the release of the major basic protein by eosinophils. The high protection rate obtained (65%) is similar to that observed previously in BALB/c mice following vaccination with irradiated larvae. Both protocols have a common factor, the high production of IL-5 and eosinophilia. However, protection occurs later in primary infected transgenic mice because specific antibodies are not yet present at the time of challenge.