Isolated Schistosoma mansoni eggs prevent allergic airway inflammation

Abstract

SummaryChronic helminth infection with Schistosoma (S.) mansoni protects against allergic airway inflammation (AAI) in mice and is associated with reduced Th2 responses to inhaled allergens in humans, despite the presence of schistosome‐specific Th2 immunity. Schistosome eggs strongly induce type 2 immunity and allow to study the dynamics of Th2 versus regulatory responses in the absence of worms. Treatment with isolated S. mansoni eggs by i.p. injection prior to induction of AAI to ovalbumin (OVA)/alum led to significantly reduced AAI as assessed by less BAL and lung eosinophilia, less cellular influx into lung tissue, less OVA‐specific Th2 cytokines in lungs and lung‐draining mediastinal lymph nodes and less circulating allergen‐specific IgG1 and IgE antibodies. While OVA‐specific Th2 responses were inhibited, treatment induced a strong systemic Th2 response to the eggs. The protective effect of S. mansoni eggs was unaltered in μMT mice lacking mature (B2) B cells and unaffected by Treg cell depletion using anti‐CD25 blocking antibodies during egg treatment and allergic sensitization. Notably, prophylactic egg treatment resulted in a reduced influx of pro‐inflammatory, monocyte‐derived dendritic cells into lung tissue of allergic mice following challenge. Altogether, S. mansoni eggs can protect against the development of AAI, despite strong egg‐specific Th2 responses.

Allergen Specific Treg Upregulated by Lung-stage Schistosome Infection Alleviates Allergic Airway Inflammation via Inhibiting IgE Secretion

“…Nonetheless, the relationship between helminths and asthma still remains. Mechanistic studies reported contradictory results, for example, one study showed that S. mansoni-mediated suppression of allergic airway in ammation was patency dependent and mediated by infection-induced Treg (21), while another study showed that protection mediated by S. mansoni egg was independent of either Treg or Breg (24). In current study, we found that lung-stage schistosome infection occurred during OVA challenge could upregulate the frequency of Treg and suppress OVA speci c IL-4 response.…”

“…Most previous studies focused on testing the preventive effect (infection before allergen sensitization) of schistosome infection against allergic asthma. And under this setting, controversial results have been reported regarding both the timing of infection (acute versus chronic) (21)(22)(23) and the effector component (egg versus worms) (24)(25)(26), which re ects the complexities of schistosome life cycle and its immune regulatory components. Moreover, contradictory results were also reported regarding the roles of regulatory T cells in schistosome mediated protection.…”

“…Moreover, contradictory results were also reported regarding the roles of regulatory T cells in schistosome mediated protection. Some studies showed that Treg was an important effector in schistosome mediated protection against asthma (21,23,(26)(27)(28), while a more recent study showed that the protection was independent of Treg (24).…”

Allergen specific Treg upregulated by lung-stage schistosome infection alleviates allergic airway inflammation via inhibiting IgE secretion

“…Mechanistic studies reported contradictory results, for example, one study showed that S. mansoni-mediated suppression of allergic airway inflammation was patency dependent and mediated by infection-induced Treg [21], while another study showed that protection mediated by S. mansoni egg was independent of either Treg or Breg [24]. In current study, we found that lung-stage schistosome infection occurred during OVA induced asthma attack could upregulate the frequency of Treg and suppressed OVA specific IL-4 response.…”

“…Most previous studies focused on testing the preventive effect (infection before allergen sensitization) of schistosome infection against allergic asthma. And under this setting, controversial results have been reported regarding both the timing of infection (acute versus chronic) [21][22][23] and the effector component (egg versus worms) [24][25][26], which reflects the complexities of schistosome life cycle and its immune regulatory components. Moreover, contradictory results were also reported regarding the roles of regulatory T cells in schistosome mediated protection.…”