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 larvae into microfilaria-producing adults in immunocompetent laboratory mice. 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 compared 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 worm persistence were equivalent in IL-4 KO and wild-type mice, the fertility and length of adult female worms in IL-4 KO mice was clearly enhanced. The high susceptibility to microfilariae in IL-4 KO mice required the presence of adult worms in a full infection cycle since microfilariae loads did not differ much between IL-4 KO and wild-type mice when purified microfilariae were injected into mice. In addition, we found that eosinophilia was diminished and immunoglobulin E (IgE) was absent in IL-4 KO mice. IgE, however, does not seem to be the essential factor for microfilarial containment since microfilaremia was not elevated in B-cell KO mice. In conclusion, IL-4 is 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 infection. IL-4 dependent effector pathways seem to operate on adult worms rather than directly on microfilariae.
Volkmann
L
L
Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.
Saeftel
M
M
Bain
O
O
Fischer
K
K
Fleischer
B
B
Hoerauf
A
A
D000818:Animals; D005260:Female; D005298:Fertility; D005368:Filariasis / Q000209:etiology*; D005370:Filarioidea / Q000502:physiology; D007073:Immunoglobulin E / Q000096:biosynthesis; D015847:Interleukin-4 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis
D015847:Interleukin-4; D009569:Nitric Oxide; D007073:Immunoglobulin E