Inflammatory diseases are on the rise in westernized countries, but also in urbanized areas of developing countries. A number of studies have now demonstrated a negative association between helminth infections and inflammatory diseases, such as allergy, suggesting a potential role for helminth-induced immune responses. However, this is not the case for all studies. In this review both supporting and opposing literature on the role of helminth infections, particularly in allergy, are discussed. Furthermore, the concept is put forward that chronic helminth infections, but not acute infections, may be associated with the expression of regulatory networks necessary for downmodulating allergic immune responses to harmless antigens. Lastly, different components of helminth-induced regulatory networks are detailed, such as the role of regulatory T and B cells, modulation of dendritic cells, the presence of suppressory alternatively activated macrophages, and their individual contributions to protection against allergic diseases. Advantage should be taken from this knowledge to identify and select individual helminth-derived molecules that may harbor therapeutic potential against inflammatory diseases.
"Inhibition or allergic airways inflammation Correlated with increased IL-10, TGFb and regulatory T cells in the lungs Park et al. (2011) Trematodes Fasicola hepatica Delays EAE onset in mice Reduction of TH1 and TH17 responses via TGFb Walsh et al. (2009) Schistosoma japonicum Attenuated CIA development in DBA/1 mice Skewing towards TH2; reduced TH17 Song et al. (2011) Schistosoma mansoni Inhibition of DSS-induced colitis Mobilization of an immunosuppressive/immunoregulatory macrophage phenotype Smith et al. (2007) Inhibition of TNBS-induced colitis in rats Modulation of colonic cytokine levels Moreels et al. (2004) Protection against anaphylaxis IL-10 producing (IL-4 deficient) B cells Mangan et al. (2004) Prevention and reversal of allergic airways inflammation in mice IL-1-producing CD1d high regulatory B cells and Foxp3 + T regulatory cells Amu et al. (2010), van der Vlugt et al. (2012) Reduction in severity of EAE in mice Suppression of IL-12p40 production Sewell et al. (2003) Prevention of T1D in NOD mice Generation of TH2 response Cooke et al. (1999) Chronic, high density infection alleviates murine allergic airway inflammation Suppression of antigen-induced cytokines; increased IL-10 from B cells and CD4 + T cells Smits and Yazdanbakhsh (2007) Suppression of CIA in mice Down-regulation of Th1 cytokines, IL-1b and NFjB in the paw; increased IL-4 and IL-10 Osada et al. (2009) S. mansoni (male cercariae) "
[Show abstract][Hide abstract] ABSTRACT: Helminth parasites are masters of immune regulation; a likely prerequisite for long-term survival by circumventing their hosts' attempt to eradicate them. From a translational perspective, knowledge of immune events as a response to infection with a helminth parasite could be used to reduce the intensity of unwanted inflammatory reactions. Substantial data have accumulated showing that inflammatory reactions that promote a variety of auto-inflammatory diseases are dampened as a consequence of infection with helminth parasites, via either the mobilization of an anti-worm spectrum of immune events or by the direct effect of secretory/excretory bioactive immunomodulatory molecules released from the parasite. However, many issues are outstanding in the definition of the mechanism(s) by which infection with helminth parasites can affect the outcome, positively or negatively, of concomitant disease. We focus on a subgroup of this complex group of metazoan parasites, the cestodes, summarizing studies from rodent models that illustrate if, and by what mechanisms, infection with tapeworms ameliorate or exaggerate disease in their host. The ability of infection with cestodes, or other classes of helminth, to worsen a disease course or confer susceptibility to intracellular pathogens should be carefully considered in the context of 'helminth therapy'. In addition, poorly characterised cestode extracts can regulate murine and human immunocyte function, yet the impact of these in the context of autoimmune or allergic diseases is poorly understood. Thus, studies with cestodes, as representative helminths, have helped cement the concept that infection with parasitic helminths can inhibit concomitant disease; however, issues relating to long-term effects, potential side-effects, mixed pathogen infections and purification of immunomodulatory molecules from the parasite remain as challenges that need to be addressed in order to achieve the use of helminths as anti-inflammatory agents for human diseases.
International journal for parasitology 10/2012; 43(3-4). DOI:10.1016/j.ijpara.2012.09.005 · 3.87 Impact Factor
"For instance, BALB/c mice exposed to Schistosoma japonicum eggs produced more IL-10 but little IL-4 (Yang et al. 2007). While mice chronically infected with Schistosoma mansoni have downregulated levels of IL-4, IL-10, IL-13 and IFN-γ (Smits and Yazdanbakhsh 2007). Moreover, in another study, infection with Schistosoma haematobium induced significant production of IL-5 and IL-10 (van den Biggelaar et al. 2000). "
"Chronic worm infections may particularly protect against allergy (4). During established infections, worms evoke strong immunoregulation, protecting themselves against host responses, for example, by eliciting regulatory cytokines such as interleukin (IL)-10 and transforming growth factor (TGF-) β. ‘Bystander’ effects of these processes may down-regulate responses to other immunogens, including allergens (5). In humans, several cross-sectional studies have demonstrated inverse associations between chronic worm infections and atopy (6,7), and initial intervention studies suggested that regular anthelminthic treatment was associated with increased skin prick reactivity (8). "
[Show abstract][Hide abstract] ABSTRACT: Allergy is commoner in developed than in developing countries. Chronic worm infections show inverse associations with allergy, and prenatal exposures may be critical to allergy risk.
To determine whether anthelminthic treatment during pregnancy increases the risk of allergy in infancy.
A randomised, double-blind, placebo-controlled trial on treatment in pregnancy with albendazole versus placebo and praziquantel versus placebo was conducted in Uganda, with a 2 × 2 factorial design; 2507 women were enrolled; infants' allergy events were recorded prospectively. The main outcome was doctor-diagnosed infantile eczema.
Worms were detected in 68% of women before treatment. Doctor-diagnosed infantile eczema incidence was 10.4/100 infant years. Maternal albendazole treatment was associated with a significantly increased risk of eczema [Cox HR (95% CI), p: 1.82 (1.26-2.64), 0.002]; this effect was slightly stronger among infants whose mothers had no albendazole-susceptible worms than among infants whose mothers had such worms, although this difference was not statistically significant. Praziquantel showed no effect overall but was associated with increased risk among infants of mothers with Schistosoma mansoni [2.65 (1.16-6.08), interaction p = 0.02]. In a sample of infants, skin prick test reactivity and allergen-specific IgE were both associated with doctor-diagnosed eczema, indicating atopic aetiology. Albendazole was also strongly associated with reported recurrent wheeze [1.58 (1.13-2.22), 0.008]; praziquantel showed no effect.
The detrimental effects of treatment suggest that exposure to maternal worm infections in utero may protect against eczema and wheeze in infancy. The results for albendazole are also consistent with a direct drug effect. Further studies are required to investigate mechanisms of these effects, possible benefits of worms or worm products in primary prevention of allergy, and the possibility that routine deworming during pregnancy may promote allergic disease in the offspring.
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