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Infection and Immunity, May 2001, p. 2950-2956, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.2950-2956.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Interleukin-4 Is Essential for the Control of Microfilariae in Murine Infection with the Filaria Litomosoides sigmodontis

Lars Volkmann,1 Michael Saeftel,1 Odile Bain,2 Kerstin Fischer,1 Bernhard Fleischer,1 and Achim Hoerauf1,*

Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany,1 and Institut de Systématique CNRS FR 1541, Biologie Parasitaire, Muséum National d'Histoire Naturelle, Paris, France2

Received 25 September 2000/Returned for modification 20 November 2000/Accepted 2 February 2001

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.

* Corresponding author. Mailing address: Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany. Phone: (49) 40-42818-301. Fax: (49) 40-42818-400. E-mail: hoerauf{at}bni.uni-hamburg.de.

Infection and Immunity, May 2001, p. 2950-2956, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.2950-2956.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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