Schistosoma mansoni in IL-4-deficient mice

Abstract

Immunopathology and immune responses to Schistosoma mansoni were examined in IL-4 -/- mice. IL-5 and IL-10 production by lymphoid cells stimulated with soluble egg antigen (SEA), peripheral eosinophilia and serum levels of soluble IL-4 receptor but not IgE were all significantly elevated over background normal levels in IL-4 -/- mice as a result of infection. Additionally, IL-10 and IL-5 in addition to IL-2 and IFN-gamma transcripts were equally evident in diseased liver tissue from infected IL-4 -/- and wild-type mice. Nevertheless, analysis of antigen-stimulated IL-2, IL-4, IL-5, IL-10 and IFN-gamma production by lymphoid organ cells from infected or egg-injected IL-4 -/- mice revealed a more Th1-like pattern of cytokine production (IFN-gamma > IL-5) than in (wild-type) mice in which a stronger type 2 response to SEA was detectable (IL-4, IL-5 > IFN-gamma). Despite this, at 8 and 16 weeks after infection, liver pathology, as indicated by the size, cellularity, cellular composition and collagen content of granulomas, was similar in IL-4 -/- and wild-type animals. As in wild-type animals, granuloma size at week 16 was smaller than at week 8, indicating that modulation had occurred in the absence of IL-4. Differences in pathology were seen only when eggs were experimentally embolized to the lungs, in which case IL-4 -/- mice made smaller granulomatous responses than did wild-type animals. These data clearly show that IL-4 is not necessary for the hepatic granuloma formation which occurs during experimental schistosomiasis.

Schistosome Infection of Transgenic Mice Defines Distinct and Contrasting Pathogenic Roles for IL-4 and IL-13: IL-13 Is a Profibrotic Agent

“…However, it is evident that IL-13 is the primary cytokine responsible for fibrosis. These data clarify the results reported for schistosome infections of STAT6-and IL-4R-deficient animals in which collagen deposition was found to be reduced (22,23) and IL-4-deficient animals in which collagen responses were normal (41). Because periportal fibrosis is a major cause of hepatic pathology in human schistosomiasis (42), regulation of IL-13 activity to limit collagen formation and deposition may have therapeutic implications.…”

Regulation of the production of soluble IL-4 receptors in murine cutaneous leishmaniasis. The roles of IL-12 and IL-4

“…These results are in agreement with a report of increased sIL-4R production in Schistosoma mansoni-infected IL-4 knock-out mice [54]; and with a report by Blum et al [55] describing the existence of two different mechanisms for sIL-4R secretion: one that is IL-4-dependent and mediated by de novo synthesis from alternatively spliced sIL-4R-specific mRNA, and an IL-4-independent mechanism, putatively mediated through shedding of membrane IL-4R.…”

Experimental models of Schistosoma mansoni infection

“…However, T cell responses were more generally affected in IL-4 ko mice (PedrasVasconcelos et al 2001). Metwali et al (1996) found granuloma size to be diminished in IL-4 ko mice but gave a different interpretation to cytokine patterns similar to those reported by Pearce et al (1996) and Chiramonte et al (1999b) found enlarged granulomas but decreased fibrosis in IL-4 ko mice. Other experiments in various strains of IL-4 ko mice have given discrepant results which we cannot yet interpret (Cheever et al 1998, Jankovic et al unpublished).…”