Chronic Helminth Infection Reduces Basophil Responsiveness in an IL-10–Dependent Manner

Abstract

Basophils play a key role in the development and effector phases of type 2 immune responses in both allergic diseases and helminth infections. This study shows that basophils become less responsive to IgE-mediated stimulation when mice are chronically infected with Litomosoides sigmodontis, a filarial nematode, and Schistosoma mansoni, a blood fluke. Although excretory/secretory products from microfilariae of L. sigmodontis suppressed basophils in vitro, transfer of microfilariae into mice did not result in basophil suppression. Rather, reduced basophil responsiveness, which required the presence of live helminths, was found to be dependent on host IL-10 and was accompanied by decreases in key IgE signaling molecules known to be downregulated by IL-10. Given the importance of basophils in the development of type 2 immune responses, these findings help explain the mechanism by which helminths protect against allergy and may have broad implications for understanding how helminth infections alter other disease states in people.

Immunologic characterization of 3 murine regimens of allergen-specific immunotherapy

“…38,39 Given that we see an increase in IL-10 levels and Treg cell numbers in our intermediate and gradual models, it is possible that suppression of basophil and mast cell function by these regulatory networks is an important mechanism of allergen tolerance in the intermediate and gradual models. Of note, an important limitation of this study was our inability to assess mast cell function in response to allergen immediately ex vivo in these different models.…”

Contribution of myeloid cell subsets to liver fibrosis in parasite infection

“…Interestingly, basophils become less responsive (evaluated by their CD200R expression and IL-4 production) to IgEmediated stimulation in mice chronically (as compared to acutely) infected with S. mansoni , primarily due to IL-10 [119]. However, their role in induction of M2, and thus in fibrosis development, was not investigated.…”

“…Having the ability to sense PAMPs, to phagocytose and to act as (APCs), these cells can promote innate parasite killing [67,118]. By secreting a number of molecules, they are generally viewed as amplifiers of the adaptive Th2/M2 immunity in helminth infection (Figure 1 [54,[75][76][77]119].…”

The Use of Filariae as a Therapeutic Agent for Hypersensitivity Diseases

“…Helminth-induced immunomodulation is multifactorial and causes suppression of both the innate and adaptive arms of the immune system (14; 144). There are multiple mechanisms by which worms are able to overcome host resistance to infection, including the induction of de novo forkhead box protein 3 expression on T cells (78) and IL-6 production (204 (114). However, functionality of mast cells and basophils in a combined allergy/helminth model has yet to be studied (55).…”