The pathways conferring immunity to human
filariases are not well known, in part because human-pathogenic filariae do not complete a full life cycle in 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 nematode Litomosoides sigmodontis. Our previous results showed that worm development is inversely correlated with Th2
cytokine production and
eosinophilia. The scope of the present study was to directly elucidate the role of
interleukin-5 (IL-5) and eosinophils in controlling the development of L. sigmodonitis after vaccination and in primary
infection. BALB/c mice immunized with 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) suppressed both blood and tissue
eosinophilia and completely abolished protection. This demonstrates, for the first time in a fully permissive filarial
infection, that
IL-5 is essential for protection induced by irradiated L3 larvae. In contrast, in primary-infected mice, anti-IL-5 treatment did not modify filarial
infection within the 1st month, most likely because during primary
infection IL-5-dependent mechanisms such as subcutaneous
eosinophilia are induced too late to disturb worm establishment. However, there is a role for
IL-5 late in primary
infection where neutrophil-dependent worm encapsulation is also under the control of
IL-5.