Neonatal Idiotypic Exposure Alters Subsequent Cytokine, Pathology, and Survival Patterns in Experimental Schistosoma mansoni Infections

Abstract

Exposure to maternal idiotypes (Ids) or antigens might predispose a child to develop an immunoregulated, asymptomatic clinical presentation of schistosomiasis. We have used an experimental murine system to address the role of Ids in this immunoregulation. Sera from mice with 8-wk Schistosoma mansoni infection, chronic (20-wk infection) moderate splenomegaly syndrome (MSS), or chronic hypersplenomegaly syndrome (HSS) were passed over an S. mansoni soluble egg antigen (SEA) immunoaffinity column to prepare Ids (8WkId, MSS Id, HSS Id). Newborn mice were injected with 8WkId, MSS Id, HSS Id, or normal mouse immunoglobulin (NoMoIgG) and infected with S. mansoni 8 wk later. Mice exposed to 8WkId or MSS Id as newborns had prolonged survival and decreased morbidity compared with mice that received HSS Id or NoMoIgG. When stimulated with SEA, 8WkId, or MSS Id, spleen cells from mice neonatally injected with 8WkId or MSS Id produced more interferon γ than spleen cells from mice neonatally injected with HSS Id or NoMoIgG. Furthermore, neonatal exposure to 8WkId or MSS Id, but not NoMoIgG or HSS Id, led to significantly smaller granuloma size and lower hepatic fibrosis levels in infected mice. Together, these results indicate that perinatal exposure to appropriate anti-SEA Ids induces long-term effects on survival, pathology, and immune response patterns in mice subsequently infected with S. mansoni.

Enhanced Interleukin-12 and CD40 Ligand Activities but ReducedStaphylococcus aureusCowan 1-Induced Responses Suggest a Generalized and Progressively Impaired Type 1 Cytokine Pattern for Human Schistosomiasis

“…Our data show that these patients not only are more susceptible to the effects of IL-10 (23) but also produce much more of the cytokine than do NC or HS patients. Nevertheless, the fact that HS patients showed no significant recovery in their SAC-or CD40L-induced IFN-␥ response when IL-10 was neutralized clearly suggests other mechanisms (20,28,29,34) may also contribute to the suppression of type-1-mediated immunity in chronic schistosomiasis.…”

“…Together, these data in addition to the murine studies mentioned above suggest that IL-10 is unlikely to be the sole mechanism responsible for downregulating type 1 cytokine responses in chronic schistosomiasis. Indeed, mechanisms involving B cells (20), anti-idiotypic antibodies (28,29), and CD8…”

Placental and Oral Delivery of Schistosoma Mansoni Antigen From Infected Mothers to Their Newborns and Children

“…13 Exposure to maternal antigens might predispose a child to develop an immunoregulated, asymptomatic clinical presentation of the infection, and may predispose them to respond with an altered, perhaps more immunoregulated, form of schistosomiasis. 4,5,14 The probably immunogenic effects of such antigens as vaccines among infected mothers and the proper time to vaccinate newborns need to be studied.…”

Parasitic diseases: opportunities and challenges in the 21st century

“…These insights will prove valuable in trying to further understand various autoimmune diseases, asthma and atopic allergies, and various immune diseases involving granuloma formation and its regulation. The delicate balance of immunoregulatory responses and maternal/perinatal immune influences can also be dissected in these chronic model systems, such as in schistosomiasis and Chagas' disease, where perinatal idiotypic and anti-idiotypic interactions are seen to be associated with subsequent levels of morbidity (Colley 1990, Montesano et al 1999). …”