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Interleukin-12 p40 secretion by cutaneous CD11c(+) and F4/80(+) cells is a major feature of the innate immune response in mice that develop Th1-mediated protective immunity to Schistosoma mansoni

Hogg, K G, Kumkate, S, Anderson, S and Mountford, A P (2003) Interleukin-12 p40 secretion by cutaneous CD11c(+) and F4/80(+) cells is a major feature of the innate immune response in mice that develop Th1-mediated protective immunity to Schistosoma mansoni. Infection and Immunity. pp. 3563-3571. ISSN 1098-5522

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Abstract

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 1alpha and interleukin-1beta (IL-1beta) 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, CD8alpha, 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 © 2003 American Society for Microbiology
Keywords: VACCINE-INDUCED IMMUNITY, DRAINING LYMPH-NODES, CYTOKINE PRODUCTION, LEISHMANIA-MAJOR, DENDRITIC CELLS, IFN-GAMMA, LYMPHOCYTES-T, IN-VITRO, SKIN, MIGRATION
Academic Units: The University of York > Biology (York)
Depositing User: Sherpa Assistant
Date Deposited: 28 Feb 2005
Last Modified: 17 Oct 2013 14:31
Published Version: http://dx.doi.org/10.1128/IAI.71.6.3563-3571.2003
Status: Published
Refereed: Yes
URI: http://eprints.whiterose.ac.uk/id/eprint/308

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