Chronic helminth infections modulate allergen-specific immune responses: Protection against development of allergic disorders?
ABSTRACT 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.
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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 · 3.40 Impact Factor
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ABSTRACT: Fasciola hepatica is a trematode that affects human and domestic ruminant health, causing significant economic losses in cattle estimated at US$2000 millon per year. Juvenile parasites migrating through the host tissues, as well as adults settle in the biliary ducts, are in contact with different cells from the immune system. Despite those interactions, the persistence of the parasite in the host for many years provides evidence of its ability to prevent or down-modulate the inflammatory response in the infection site. Different strategies have been developed by the parasite to prevent potential damage being induced by the immune response, thus allowing some parasites to reach the adult stage in a safe place such as the biliary ducts. In this review we discuss how excretory-secretory products (ESP) from F. hepatica can affect the functionality of pivotal immune cells, such as eosinophils and macrophages by inducing selective apoptosis pathways and alternative activation of macrophages. Furhermore, the modulatory effects of ESP on dendritic cell activation and lymphocyte proliferation is reviewed as a strategy to facilitate F. hepatica evasion of both innate and adaptive immunity.Current Immunology Reviews 11/2009; 5(4). DOI:10.2174/157339509789503961