IL-5 is essential for vaccine-induced protection and for resolution of primary infection in murine filariasis

The pathways conferring immunity to human filariases are not well known, in part because human-pathogenic filariae do not complete a full life cycle i n laboratory mice. We have used the only fully permissive infection of mice with filariae, i.e., infection of BALB/c mice with the rodent filarial nem atode Litomosoides sigmodontis. Our previous results showed that worm devel opment is inversely correlated with Th2 cytokine production and eosinophili a. The scope of the present study was to directly elucidate the role of int erleukin-5 (IL-5) and eosinophils in controlling the development of L. sigm odontis after vaccination and in primary infection. BALB/c mice immunized w ith irradiated third-stage larvae (L3) were confirmed to have elevated IL-5 levels as well as high subcutaneous eosinophilia and to attack and reduce incoming larvae within the first 2 days, resulting in 70% reduction of worm load. Treatment of vaccinated mice with anti-IL-5 antibody (TRFK-5) suppre ssed both blood and tissue eosinophilia and completely abolished protection . This demonstrates, for the first time in a fully permissive filarial infe ction, that IL-5 is essential for protection induced by irradiated L3 larva e. In contrast, in primary-infected mice, anti-IL-5 treatment did not modif y filarial infection within the Ist month, most likely because during prima ry infection IL-5-dependent mechanisms such as subcutaneous eosinophilia ar e induced too late to disturb worm establishment. However, there is a role for IL-5 late in primary infection where neutrophil-dependent worm encapsul ation is also under the control of IL-5.