Prevention of Type 1 diabetes through parasite infection

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From: Immunotherapy(Vol. 7, Issue 6)
Publisher: Future Medicine Ltd.
Document Type: Editorial; Report
Length: 2,661 words
Lexile Measure: 2020L

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Author(s): Patricia Méndez-Samperio [*] aff1 , Jorge Luis de-la-Rosa-Arana aff2

Keywords:

helminths; immunomodulatory pathways; Type 1 diabetes

Type 1 diabetes is a chronic progressive autoimmune disease in which the pancreatic [beta] cells are selectively destroyed by pathogenic IFN-[gamma]-producing T-helper (Th)1 cells, CD8+ T cells and macrophages [1 ]. The development of this disease is influenced by environmental factors in genetically susceptible subjects [2 ]. At present, the incidence of Type 1 diabetes is increasing in several developed countries [3 ]. The 'hygiene hypothesis', first postulated by Strachan in 1989 [ 4 ], could be one possible explanation of an increase in this disease prevalence in developing countries. Recently, an extension of this hypothesis suggests that improved hygiene, vaccination, and greater access to antibiotics may increase susceptibility to some autoimmune diseases [ 5 ]. Moreover, several studies have provided support for this demonstrating, in animal models, that infection with parasite antigens modulate the activity of the immunity and induce the inhibition of autoimmune Type 1 diabetes [ 6-8 ]. In addition, cross-sectional human studies in southern India showed an inverse association between Type 1 diabetes diabetes with lymphatic filariasis [9 ].

How does parasite infection protect against Type 1 diabetes?

To date, the immunoregulatory pathways of parasites to control the onset of Type 1 diabetes remain largely undefined. Chronic helminth infection induces a wide range of immunomodulation mainly characterized by dominant Th 2 type immune responses, and can modulate the host's adaptive immune responses by induction of T-regulatory cells (Tregs) or secretion of the anti-inflammatory cytokines, IL-10 and TGF-[beta] [10 ]. Some studies indicate that parasite infection can prevent onset of diabetes through immune pathways involving at least, invariant natural killer T (iNKT) cells, Tregs, and a direct effect of the anti-inflammatory cytokines such as IL-10 and TGF-[beta]. Regarding an important role of iNKT cells in prevention of Type 1 diabetes, it has been reported that in both human and mice, increased number of iNKT cells prevented Type 1 diabetes [11 ]. In support of this, Zaccone et al . [12 ] reported that prevention of diabetes in nonobese diabetic (NOD) mice by Schistosoma mansoni antigens is highly associated with an increased number of iNKT cells.

Evidence that Tregs could be involved in the regulation of immunity and protection against Type 1 diabetes comes from studies showing that in both humans and mice, decreased function of natural Tregs correlates with the development of diabetes [13,14 ]. In contrast, Brode et al . [15 ] showed that prevention of cyclophosphamide-induced diabetes is associated with the reduction of Tregs. However, the concept that Tregs are implicated in control of autoimmune diabetes is supported by a report which demonstrated that the prevention of diabetes through S. mansoni egg antigens is associated with increased numbers of Tregs [16 ]. Furthermore, Everts et al . [17 ] showed that transfer of helminth-specific Tregs or increase of endogenous Tregs by IL-2 administration prevents the onset of diabetes in NOD mice. The main immunological mechanisms used by Tregs to prevent diabetes are by expressing high levels...

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Gale Document Number: GALE|A422428336