Abstract
The continual rise of asthma in industrialised countries stands in strong contrast to the situation in developing lands. According to the modified Hygiene Hypothesis, helminths play a major role in suppressing bystander immune responses to allergens, and both epidemiological and experimental studies suggest that the tropical parasitic trematode Schistosoma mansoni elicits such effects. The focus of this study was to investigate which developmental stages of schistosome infection confer suppression of allergic airway inflammation (AAI) using ovalbumin (OVA) as a model allergen. Moreover, we assessed the functional role and localization of infection-induced CD4+Foxp3+ regulatory T cells (Treg) in mediating such suppressive effects. Therefore, AAI was elicited using OVA/adjuvant sensitizations with subsequent OVA aerosolic challenge and was induced during various stages of infection, as well as after successful anti-helminthic treatment with praziquantel. The role of Treg was determined by specifically depleting Treg in a genetically modified mouse model (DEREG) during schistosome infection. Alterations in AAI were determined by cell infiltration levels into the bronchial system, OVA-specific IgE and Th2 type responses, airway hyper-sensitivity and lung pathology. Our results demonstrate that schistosome infection leads to a suppression of OVA-induced AAI when mice are challenged during the patent phase of infection: production of eggs by fecund female worms. Moreover, this ameliorating effect does not persist after anti-helminthic treatment, and depletion of Treg reverts suppression, resulting in aggravated AAI responses. This is most likely due to a delayed reconstitution of Treg in infected-depleted animals which have strong ongoing immune responses. In summary, we conclude that schistosome-mediated suppression of AAI requires the presence of viable eggs and infection-driven Treg cells. These data provide evidence that helminth derived products could be incorporated into treatment strategies that specifically target suppression of immune responses in AAI by inducing Treg cells.
Highlights
Over the last century and in strong contrast to third world countries, Western populations have shown a consistent rise in autoimmune disorders (e.g. Crohn’s disease) and allergic conditions such as asthma [1]
The evidence provided by epidemiological surveys and experimental animal models has been so overwhelming that such helminths are included in the Hygiene Hypothesis
Since helminths provoke immunological responses that are similar to those seen in allergy it is suggested that additional mechanisms dampen such allergic responses
Summary
Over the last century and in strong contrast to third world countries, Western populations have shown a consistent rise in autoimmune disorders (e.g. Crohn’s disease) and allergic conditions such as asthma [1]. In essence, this hypothesis states that due to well-established sanitation and vaccination procedures, the overall reduction in common Th1-inducing (bacterial and viral) infections has resulted in a decreased ability to immunologically counterbalance Th2-driven diseases. This hypothesis states that due to well-established sanitation and vaccination procedures, the overall reduction in common Th1-inducing (bacterial and viral) infections has resulted in a decreased ability to immunologically counterbalance Th2-driven diseases This has created a conundrum, since a large body of epidemiological evidence and research has established that helminth diseases, which are strong Th2 inducers themselves, protect against developing allergic responses [4].
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