Helminth Infection Protects Mice from Anaphylaxis via IL-10-Producing B Cells

Abstract

Modulation of the immune system by infection with helminth parasites, including schistosomes, is proposed to reduce the levels of allergic responses in infected individuals. In this study we investigated whether experimental infection with Schistosoma mansoni could alter the susceptibility of mice to an extreme allergic response, anaphylaxis. We formally demonstrate that S. mansoni infection protects mice from an experimental model of systemic fatal anaphylaxis. The worm stage of infection is shown to mediate this protective effect. In vivo depletion studies demonstrated an imperative role for B cells and IL-10 in worm-mediated protection. Furthermore, worm infection of mice increases the frequency of IL-10-producing B cells compared with that in uninfected mice. However, transfer of B cells from worm-infected mice or in vitro worm-modulated B cells to sensitized recipients exacerbated anaphylaxis, which was attributed to the presence of elevated levels of IL-4-producing B cells. Worm-modulated, IL-10-producing B cells from IL-4-deficient, but not IL-5-, IL-9- or IL-13-deficient, mice conferred complete resistance to anaphylaxis when transferred to naive mice. Therefore, we have dissected a novel immunomodulatory mechanism induced by S. mansoni worms that is dependent on an IL-10-producing B cell population that can protect against allergic hypersensitivity. These data support a role for helminth immune modulation in the hygiene hypothesis and further illustrate the delicate balance between parasite induction of protective regulatory (IL-10) responses and detrimental (IL-4) allergic responses.

A Helminth Immunomodulator Reduces Allergic and Inflammatory Responses by Induction of IL-10-Producing Macrophages

“…The importance of IL-10 in cystatin-induced protection against asthma is in accordance with reports that IL-10 modulates allergic immune responses in mice infected with the gut nematode Heligmosomoides polygyrus or the blood fluke Schistosoma mansoni (39,40). However, other studies demonstrate that helminth-induced protection against allergic disease is not dependent on IL-10 and they propose a role for TGF-␤ (6, 41).…”

“…However, depletion of Treg cells by anti-CD25 treatment did not lead to reduction of IL-10 levels in our experiments, strongly suggesting that Treg cells are not the main source of IL-10 in our setting. Interestingly, in other infections such as toxoplasmosis or schistosomiasis, Th1 cells or B cells are shown to be the relevant IL-10 sources (40,50). Because our depletion experiments revealed that Treg cells contribute to the lowering of eosinophil numbers and OVA-specific IgE production, we suggest that IL-10-independent Treg cell functions could have a role in the antiallergic effect of cystatin (51,52).…”

Lack of antigen-specific Th1 response alters granuloma formation and composition inSchistosoma mansoni-infected MyD88-/- mice

“…Furthermore, the T cell responses were independent of IL-12p40 production since we were not able to detect this cytokine in the culture supernatants (data not shown). With regards to the increased IL-10 production by MyD88 -/-T cells, this phenomenon cannot be explained by contaminating primed B cells which were recently shown to strongly elevate IL-10 in a bulk spleen cell assay [16], as also observed in Fig. 5C.…”

Regulatory B Cells and Allergy: Uncovering the Link

“…Thus, helminth infections can contribute to an immunoregulatory environment and promote both dampening of T H 1-, T H 17,-and T H 2-skewed diseases [12]. Infection with S mansoni proved to be protective in an experimental model of systemic anaphylaxis [18]. This effect was dependent on induction of IL-10-producing B cells, which increased 2-fold in S mansoni-infected mice and can protect against allergic hypersensitivity [18].…”