Numerous population studies and experimental models suggest that helminth infections can ameliorate immuno-inflammatory disorders such as asthma and autoimmunity. Immunosuppressive cell populations associated with helminth infections include Treg and alternatively-activated macrophages. In previous studies, we showed that both CD4+CD25+ Treg, and CD4– MLN cells from Heligmosomoides polygyus-infected C57BL/6 mice were able to transfer protection against allergic airway inflammation to sensitized but uninfected animals. We now show that CD4–CD19+ MLN B cells from infected, but not naïve, mice are able to transfer a down-modulatory effect on allergy, significantly suppressing airway eosinophilia, IL-5 secretion and pathology following allergen challenge. We further demonstrate that the same cell population can alleviate autoimmune-mediated inflammatory events in the CNS, when transferred to uninfected mice undergoing myelin oligodendrocyte glycoprotein(p35–55)-induced EAE. In both allergic and autoimmune models, reduction of disease was achieved with B cells from helminth-infected IL-10−/− donors, indicating that donor cell-derived IL-10 is not required. Phenotypically, MLN B cells from helminth-infected mice expressed uniformly high levels of CD23, with follicular (B2) cell surface markers. These data expand previous observations and highlight the broad regulatory environment that develops during helminth infections that can abate diverse inflammatory disorders in vivo.

Allergic asthma is less prevalent in countries with parasitic helminth infections, and mice infected with parasites such as Heligmosomoides polygyrus are protected from allergic airway inflammation. To establish whether suppression of allergy could be mediated by soluble products of this helminth, we tested H. polygyrus excretory-secretory (HES) material for its ability to impair allergic inflammation. When HES was added to sensitising doses of ovalbumin, the subsequent allergic airway response was suppressed, with ablated cell infiltration, a lower ratio of effector (CD4 + CD25 + Foxp3 − ) to regulatory (CD4 + Foxp3 + ) T (Treg) cells, and reduced Th1, Th2 and Th17 cytokine production. HES exposure reduced IL-5 responses and eosinophilia, abolished IgE production and inhibited the type 2 innate molecules arginase-1 and RELM-α (resistin-like molecule-α). Although HES contains a TGF-β-like activity, similar effects in modulating allergy were not observed when administering mammalian TGF-β alone. HES also protected previously sensitised mice, suppressing recruitment of eosinophils to the airways when given at challenge, but no change in Th or Treg cell populations was apparent. Because heat-treatment of HES did not impair suppression at sensitisation, but compromised its ability to suppress at challenge, we propose that HES contains distinct heat-stable and heat-labile immunomodulatory molecules, which modulate pro-allergic adaptive and innate cell populations.Keywords: Allergy r Eosinophils r IgE r Infection r Macrophages IntroductionAllergic asthma has dramatically increased in prevalence in developing countries, exceeding 5% of the Western European and North American populations [1]. This contrasts with much lower asthma incidence in tropical countries that have significant levels of parasite infections, and these observations have stimulated research into the effects of parasitic organisms on human allergy [2][3][4]. From these studies, it has emerged that allergic diseases are least common in parts of the world with high helminth endemicity, and that within endemic populations the prevalence of atopy is significantly lower in individuals with chronic worm infections [5][6][7][8][9][10].Correspondence: Dr. Rick M. Maizels e-mail: rick.maizels@ed.ac.ukWhile a causal link between human helminth infections and reduced allergy has yet to be proven [2], chemotherapeutic clearance of intestinal helminths can result in accentuated atopic responsiveness [11][12][13] and helminth infection blocks overt allergy in a number of animal models [14][15][16][17]. The degree to which helminths may influence allergy, however, is clearly variable between different parasite species [18], and is probably dependent upon the duration and intensity of infection [2,19], each factors that need to be taken into account in assessing this interaction.The concept that helminths may act in a beneficial way for therapy of immunological disorders is one that has been gaining * These author contributed equally to this work. Eur. J. Immunol. 20...

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