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.
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.
Hogg
Karen G
KG
Department of Biology (Area 5), The University of York, United Kingdom.
Kumkate
Supeecha
S
Anderson
Sonia
S
Mountford
Adrian P
AP
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis*; D039521:CD11c Antigen / Q000032:analysis*; D005260:Female; D007375:Interleukin-1 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6 / Q000096:biosynthesis; D007814:Larva / Q000528:radiation effects; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D021122:Protein Subunits / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology; D012550:Schistosoma mansoni / Q000276:immunology* / Q000528:radiation effects; D012867:Skin / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D051193:Toll-Like Receptors; D014611:Vaccination
D000943:Antigens, Differentiation; D039521:CD11c Antigen; D007375:Interleukin-1; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D021122:Protein Subunits; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; C036763:monocyte-macrophage differentiation antigen; D018664:Interleukin-12