Disruption of interleukin-27 signaling results in impaired gamma interferon production but does not significantly affect immunopathology in murine schistosome infection.
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.
Shainheit
Mara G
MG
Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.
Saraceno
Rosita
R
Bazzone
Lindsey E
LE
Rutitzky
Laura I
LI
Stadecker
Miguel J
MJ
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*
D020381:Interleukin-17; D007378:Interleukins; D007371:Interferon-gamma