Signaling via interleukin-4 receptor alpha chain is required for successful vaccination against schistosomiasis in BALB/c mice.
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.
Mountford
A P
AP
Department of Biology, The University of York, York, United Kingdom. apm10@york.ac.uk
Hogg
K G
KG
Coulson
P S
PS
Brombacher
F
F
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D018664:Interleukin-12 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019948:Receptors, Interleukin-4 / Q000502:physiology*; D012552:Schistosomiasis / Q000276:immunology*; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology; D014611:Vaccination
D016207:Cytokines; D007074:Immunoglobulin G; D019948:Receptors, Interleukin-4; D018664:Interleukin-12