Schistosomiasis Decreases Central Nervous System Inflammation and Alters the Progression of Experimental Autoimmune Encephalomyelitis

Abstract

A preestablished infection with the parasitic helminth, Schistosoma mansoni, significantly reduced the incidence and delayed the onset of experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice immunized with myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide. The altered disease progression was not solely due to the induction of a strong Th2 response, since intraperitoneal injection of schistosome eggs did not affect disease development. MOG-specific gamma interferon (IFN-␥), nitric oxide, and tumor necrosis factor alpha production by splenocytes was significantly reduced in schistosome-infected mice compared to uninfected mice. However, similar levels of interleukin-10 (IL-10) were produced in an antigen-specific manner, suggesting that the induction of antigen-specific responses was not inhibited. Analysis of in vivo cytokine production by real-time PCR indicated that IL-12p40, but not IFN-␥, transcript levels were dramatically reduced in the spinal cords of schistosome-infected, MOG-immunized mice. Furthermore, analysis of the cellular composition of the spinal cords and brains revealed that a preestablished infection with S. mansoni decreased central nervous system (CNS) inflammation, particularly of macrophages and CD4 T cells. These results suggest that schistosomiasis may negatively regulate the onset of EAE by downregulating the production of proinflammatory cytokines and altering CNS inflammation.

Schistosoma mansoni antigen-driven interleukin-10 production in infected asthmatic individuals

“…mansoni infection seems to be protective against asthma (Medeiros et al 2003, Araujo et al 2004. Using mice models of S. mansoni infection it has been demonstrated that this parasite also protects against the development of auto-immune disease such as diabetes, experimental auto-immune encephalopathy, and Crohn's disease (Cooke et al 1999, Elliott et al 2003, La Flamme et al 2003, Sewell et al 2003, Zaccone et al 2003. Some of these studies suggest that IL-10 is a key cytokine involved in the modulation of the inflammatory immune response observed in these diseases.…”

Schistosoma mansoni infection modulates the immune response against allergic and auto-immune diseases

“…mansoni infection also decreased tissue damage and clinical manifestation of others Th1-mediated autoimmune diseases such as multiple sclerosis and Crohn's disease. In a mice model to study experimental autoimmune encephalite (EAE), a multiple sclerosis like disease, it was demonstrated that infection with S. mansoni delays the onset of the disease and prevents inflammation in the central nervous system (La Flamme et al 2003, Sewell et al 2003). Attenuation of the clinical course of EAE was followed by a reduction in the synthesis of pro-inflammatory mediators, such as IFN-γ, TNF-α and NO, by spleen and central nervous cells in vitro, while the levels of IL-4 and IL-5 in plasma were, as predicted, higher in the parasite-infected group (La Flamme et al 2003).…”

“…In a mice model to study experimental autoimmune encephalite (EAE), a multiple sclerosis like disease, it was demonstrated that infection with S. mansoni delays the onset of the disease and prevents inflammation in the central nervous system (La Flamme et al 2003, Sewell et al 2003). Attenuation of the clinical course of EAE was followed by a reduction in the synthesis of pro-inflammatory mediators, such as IFN-γ, TNF-α and NO, by spleen and central nervous cells in vitro, while the levels of IL-4 and IL-5 in plasma were, as predicted, higher in the parasite-infected group (La Flamme et al 2003). Although the production of IL-10 did not differ between mice that were infected or not with S. mansoni in this study, in the EAE S. mansoni ova immunization lead to production of IL-10 and TGF-β, in addition to IL-4, by spleen cells in vitro, and decreased IFN-γ synthesis (Sewell et al 2003).…”

“…Among the environmental factors, low socio-economic status (Patterson et al 1996, von Mutius et al 1994, Staines et al 1997a, Blanchard et al 2001, and the presence of infections have been implicated in protecting people against allergic (Lynch et al 1993, Araujo et al 2000, Cooper et al 2003, Medeiros et al 2003 and autoimmune diseases (Cooke et al 1999, Kurtzke 2000, La Flamme et al 2003. Recently, there has been growing interest in the hypothesis that infections might play a role in preventing or suppressing auto-immune and allergic disorders as studies have revealed that the prevalence of allergies and auto-immune diseases are increasing in developed countries, in conjunction with improved hygienic conditions.…”

Protection from EAE by IL‐4Rα−/− macrophages depends upon T regulatory cell involvement

“…Our study does not distinguish between the contribution of macrophages, microglia and neutrophils, but because lymphocytes and macrophages were the predominant cells infiltrating the CNS and from our previous results on the function of alternatively activated macrophages, 27,36 we suspect macrophages to be the principal effector cells. Furthermore, interactions between infiltrating macrophages and T cells are believed to be responsible for microglial activation, and it has been demonstrated that microglia are not appropriately activated in the absence of blood-borne macrophages.…”