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Signaling via interleukin-4, receptor alpha chain is required for successful vaccination against schistosomiasis in BALB/c mice

Mountford, A.P., Coulson, P.S., Hogg, K.G. and Brombacher, F. (2001) Signaling via interleukin-4, receptor alpha chain is required for successful vaccination against schistosomiasis in BALB/c mice. Infection and Immunity. pp. 228-236. ISSN 1098-5522

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Radiation-attenuated (RA) schistosome larvae are potent stimulators of innate immune responses at the skin site of exposure (pinna) that are likely to be important factors in the development of Th1-mediated protective immunity. In addition to causing an influx of neutrophils, macrophages, and dendritic cells (DCs) into the dermis, RA larvae induced a cascade of chemokine and cytokine secretion following in vitro culture of pinna biopsy samples. While macrophage inflammatory protein 1 and interleukin-1 (IL-1) were produced transiently within the first few days, the Th1-promoting cytokines IL-12 and IL-18 were secreted at high levels until at least day 14. Assay of C3H/HeJ mice confirmed that IL-12 secretion was not due to lipopolysaccharide contaminants binding Toll-like receptor 4. Significantly, IL-12 p40 secretion was sustained in pinnae from vaccinated mice but not in those from nonprotected infected mice. In contrast, IL-10 was produced from both vaccinated and infected mice. This cytokine regulates IL-12-associated dermal inflammation, since in vaccinated IL-10/ mice, pinna thickness was greatly increased concurrent with elevated levels of IL-12 p40. A significant number of IL-12 p40 cells were detected as emigrants from in vitro-cultured pinnae, and most were within a population of rare large granular cells that were Ia, consistent with their being antigen-presenting cells. Labeling of IL-12 cells for CD11c, CD205, CD8, CD11b, and F4/80 indicated that the majority were myeloid DCs, although a proportion were CD11c F4/80, suggesting that macrophages were an additional source of IL-12 in the skin.

Item Type: Article
Copyright, Publisher and Additional Information: Copyright © 2001 American Society for Microbiology
Institution: The University of York
Academic Units: The University of York > Biology (York)
Depositing User: Sherpa Assistant
Date Deposited: 28 Feb 2005
Last Modified: 18 Apr 2016 17:57
Published Version: http://dx.doi.org/10.1128/IAI.69.1.228-236.2001
Status: Published
Refereed: Yes
URI: http://eprints.whiterose.ac.uk/id/eprint/310

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