Interleukin-4 is essential for the control of microfilariae in murine infection with the filaria Litomosoides sigmodontis

Litomosoides sigmodontis is the only filaria which develops from infective lan:ae into microfilaria-producing adults in immunocompetent laboratory mic e. In this study we report that interleukin-4 knockout (IL-4 KO) mice have an up to 100-fold-higher and a significantly prolonged microfilaremia compa red to wild-type BALB/c mice! as well as 20 times more microfilariae in the thoracic cavity, the site of infection. While worm development and adult w orm persistence were equivalent in IL-4 KO and wild-type mice, tie fertilit y and length of adult female worms in IL-4 KO mice was clearly enhanced. Th e high susceptibility to microfilariae in IL-4 KO mice required the presenc e of adult worms in a full infection cycle since microfilariae loads did no t differ much between IL-4 KO and wild-type mice when purified microfilaria e were injected into mice. In addition, we found that eosinophilia was dimi nished and immunoglobulin E (IgE) was absent in IL-4 KO mice, IgE, however, does not seem to be the essential factor for microfilarial containment sin ce microfilaremia was not elevated in B cell KO mice. In conclusion, IL-4 i s shown for the first time to be essential for the control of microfilarial loads but not of adult worm loads in a fully permissive murine filarial in fection, IL-4 dependent effector pathways seem to operate on adult worms ra ther than directly on microfilariae.