The granulomatous response in murine Schistosomiasis mansoni does not switch to Th1 in IL-4-deficient C57BL/6 mice.
IL-4 plays an important role in polarizing inflammation toward a Th2 response. It remains uncertain, however, whether IL-4 also serves to prevent expression of Th1 inflammation. Therefore, using a genetically pure C57BL/6 IL-4-deficient mouse, we studied the role of IL-4 in regulating the production of IFN-gamma and Th1 inflammation in the granulomas of mice infected with Schistosoma mansoni. In contrast to normal animals, IL-4 mutant mice generated smaller liver granulomas that contained fewer eosinophils and no mast cells. Collagenase-dispersed granuloma cells were analyzed by flow cytometry and cultured in vitro to measure cytokine and Ig production. Compared with control granuloma cells, IL-4-/- cells secreted only small quantities of IL-5 and IL-10. Also, there was impaired expression of the IL-4-dependent molecules IgE and IgG1 as well as B cell surface class II and CD23. Yet the granulomas of IL-4 -/- animals produced little IFN-gamma, IgG2a, or other molecules associated with Th1 inflammation even after Ag or anti-CD3 stimulation. Splenocytes from IL-4 -/- animals stimulated with schistosome Ag also failed to produce a Th1 response. Our data show that most aspects of the Th2 response in murine schistosomiasis are highly dependent on IL-4 production. But in the absence of IL-4, neither the natural local granulomatous response to schistosome ova nor the systemic response to soluble egg Ag switches to the type 1 phenotype. Thus the production of IL-4 early in the inflammatory response is not the only factor preventing Th1 expression in inflammation.
Metwali
A
A
Department of Internal Medicine, University of Iowa, Iowa City 52242, USA.
Elliott
D
D
Blum
A M
AM
Li
J
J
Sandor
M
M
Lynch
R
R
Noben-Trauth
N
N
Weinstock
J V
JV
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D006099:Granuloma / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D015847:Interleukin-4 / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D018417:Th1 Cells / Q000276:immunology*
D015847:Interleukin-4