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Infection and Immunity, June 2003, p. 3563-3571, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3563-3571.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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

Karen G. Hogg, Supeecha Kumkate, Sonia Anderson, and Adrian P. Mountford*

Department of Biology (Area 5), The University of York, York YO10 5YW, United Kingdom

Received 21 November 2002/ Returned for modification 3 February 2003/ Accepted 12 March 2003

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{alpha} and interleukin-1ß (IL-1ß) 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{alpha}, 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.

* Corresponding author. Mailing address: Department of Biology (Area 5), P.O. Box 373, The University of York, York YO10 5YW, United Kingdom. Phone: 44 1904 328595. Fax: 44 1904 328599. E-mail: apm10{at}york.ac.uk.

Editor: W. A. Petri, Jr.

Infection and Immunity, June 2003, p. 3563-3571, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3563-3571.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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