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Infect. Immun. doi:10.1128/IAI.01053-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Disruption of IL-27 signaling results in impaired IFN- production but does not significantly affect immunopathology in murine schistosome infection

Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA

^* To whom correspondence should be addressed. Email: miguel.stadecker{at}tufts.edu.

	Abstract

In schistosomiasis mansoni, parasite eggs precipitate hepato-intestinal granulomatous inflammation and fibrosis mediated by CD4 T cells specific for egg antigens. Severity of disease varies extensively in humans and among mouse strains. Marked disease exacerbation induced in typically low pathology C57BL/6 mice by immunization with schistosome egg antigens (SEA) in CFA (SEA/CFA), correlates with elevated production of the pro-inflammatory cytokines IFN- and IL-17, which are regulated by IL-12 and IL-23, respectively. We now examined the effect on the schistosome infection by a third member of the IL-12 family of heterodimeric cytokines, IL-27, using SEA/CFA-immunized and unimmunized mice deficient in the IL-27 receptor chain WSX-1 (WSX-1^-/-). SEA-stimulated bulk mesenteric lymph node cells or CD4 T cells from 7 week-infected WSX-1^-/- mice produced significantly less IFN- than those from C57BL/6 mice even though there was no difference between these mice in the exacerbated hepatic egg-induced granulomatous inflammation, or in levels of IL-17, induced by immunization with SEA/CFA. A fraction of the cells in the granulomas stained positive for IL-27, but there were no significant differences between WSX-1^-/-and BL/6 mice, nor were there differences in the number of CD4 T cells and eosinophils. A 24 week-long chronic infection revealed markedly reduced levels of pro-inflammatory cytokines with IFN- also lower in WSX-1^-/- mice, but again the magnitude of immunopathology was not significantly different between the two groups. These findings indicate that despite the impaired IFN- production, IL-27 signaling has no significant effect on either the magnitude of egg-induced immunopathology, or on its closest in vitro correlate, IL-17.

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