title: Disruption of interleukin-27 signaling results in impaired gamma interferon production but does not significantly affect immunopathology in murine schistosome infection.
abstract: In schistosomiasis mansoni, parasite eggs cause hepatointestinal granulomatous inflammation and fibrosis mediated by CD4 T cells specific for egg antigens. The 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 complete Freund's adjuvant (SEA/CFA) correlates with elevated production of the proinflammatory cytokines gamma interferon (IFN-gamma) and interleukin-17 (IL-17), which are regulated by IL-12 and IL-23, respectively. Here we examined the effect on the schistosome infection of 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-gamma than did those from C57BL/6 mice, even though there was no difference between these mice in exacerbated hepatic egg-induced granulomatous inflammation or in the 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 chronic infection resulted in markedly reduced levels of proinflammatory cytokines, including IFN-gamma, 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-gamma 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.
authors.affiliation: Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Mara G
authors.initials: MG
authors.lastname: Shainheit
authors.forename: Rosita
authors.initials: R
authors.lastname: Saraceno
authors.forename: Lindsey E
authors.initials: LE
authors.lastname: Bazzone
authors.forename: Laura I
authors.initials: LI
authors.lastname: Rutitzky
authors.forename: Miguel J
authors.initials: MJ
authors.lastname: Stadecker
mesh_terms: D000818:Animals; D007249:Inflammation / Q000517:prevention & control; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D020381:Interleukin-17 / Q000032:analysis / Q000172:deficiency / Q000502:physiology*; D007378:Interleukins / Q000032:analysis; D051379:Mice; D012550:Schistosoma mansoni; D012552:Schistosomiasis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D007371:Interferon-gamma