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Infection and Immunity, January 2001, p. 228-236, Vol. 69, No. 1
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.1.228-236.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Signaling via Interleukin-4 Receptor alpha  Chain Is Required for Successful Vaccination against Schistosomiasis in BALB/c Mice

Adrian P. Mountford,1,* Karen G. Hogg,1 Patricia S. Coulson,1 and Frank Brombacher2

Department of Biology, The University of York, York, United Kingdom,1 and Department of Immunology, Health Faculty, University of Cape Town, Cape Town, South Africa2

Received 10 July 2000/Returned for modification 19 August 2000/Accepted 25 September 2000

Although protective immunity in C57BL/6 mice induced by a single dose of the radiation-attenuated schistosome vaccine is believed to be mediated by Th1-type immune responses, we here report that in BALB/c mice protection can also depend upon signaling via the interleukin-4 (IL-4) receptor which conventionally governs the development of Th2-type immune responses. We show that in BALB/c mice deficient for the IL-4 receptor alpha  chain (IL-4Ralpha -/-), which are unresponsive to IL-4 and IL-13, vaccine-induced protection is abrogated compared with that in wild-type (WT) mice. In vaccinated IL-4Ralpha -/- mice, IL-12p40 production by cells from the skin exposure site was elevated, although gamma interferon (IFN-gamma ) production in draining lymphoid tissues was similar in WT and IL-4Ralpha -/- mice. Nevertheless, the effector response in IL-4Ralpha -/- mice was Th1 biased with elevated IFN-gamma in the lungs and higher immunoglobulin G2a (IgG2a) and IgG2b titers but negligible quantities of Th2-associated IgG1 and IgE. Interestingly, levels of IL-4 were equivalent in WT and IL-4Ralpha -/- mice, indicating that Th2 responses were not dependent upon signaling by IL-4 or IL-13. No differences in the phenotype and composition of the pulmonary effector mechanism that might explain the failure to induce protection in IL-4Ralpha -/- mice were detected. However, passive transfer of partial protection to naive IL-4Ralpha -/- mice, using serum from vaccinated WT mice, indicates that Th2-associated antibodies such as IgG1 have a role in parasite elimination in BALB/c strain mice and that signaling via IL-4R can be an important factor in the generation of protection.

* Corresponding author. Mailing address: Department of Biology, The University of York, P.O. Box 373, York YO10 5YW, United Kingdom. Phone: 44 1904 4343 88. Fax: 44 1904 432884. E-mail: apm10{at}york.ac.uk.

Infection and Immunity, January 2001, p. 228-236, Vol. 69, No. 1
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.1.228-236.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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Copyright © 2001 by the American Society for Microbiology. All rights reserved.