Volume 28, Number 10, October 2006 Parasitic worms and inﬂammatory diseases Table 2 Diabetes (Type 1 and 2) incidences by region for the year 2003 and projected incidences for the year 2025 (Type 1 and type 2). Ages 20–79 2003 2025 Population (million) No. of people with diabetes (million) Prevalence (%) Population (million) No. of people with diabetes (million) Prevalence (%) Region Europe North America Africa Western Paciﬁc East Mediterraneanand Middle East South and Central America South East Asia Total 621 290 295 1384 276 252 705 3823 48·4 23·0 7·1 43·0 19·2 14·2 39·3 194 Adapted from the IDF e-Atlas, http://www.eatlas.idf.org/, © International Diabetes Federation, Brussels. 7·8 7·9 2·4 3·1 7·0 5·6 5·6 5·1 646 374 541 1751 494 364 1081 5251 58·6 36·2 15·0 75·8 39·4 26·2 81·6 333 9·1 9·7 2·8 4·3 8·0 7·2 7·5 6·3 triggering both Th1- and Th2-like responses could delay or abolish autoimmune pathology in NOD mice (see Table 3). The NOD mouse appears to be a good model for testing the predictions of the Hygiene Hypothesis, therefore we have used it to study the effects of bacterial and helminth infection on the onset of T1D. Schistosoma mansoni infection, or even exposure to antigens derived from this helminth, results in long-lasting prevention of diabetes characterized by a strong Th2 response (31,32). S. mansoni protection appears to stem largely from a shift to a non-pathological Th2 response, although there is also evidence for the generation of immunosuppressive regulatory cells (Treg) (32). Essentially similar results have been observed using two other species of helminth, Heligmosomoides polygyrus and Trichinella spiralis (C. Lawrence, unpublished data). Similarly, infection of NOD mice with live attenuated Salmonella bacteria induces a long-lasting protection from T1D (35). Prevention of a Th1- mediated autoimmune disease such as T1D by infection with a classic Th1-stimulating pathogen appears rather paradoxical. Potentially a generalized Salmonella-induced IFN-γ release may mediate suppression through its effects on the innate immune system, particularly DC, but the mechanism awaits full characterization (our unpublished observations). At any rate, the invocation of a simple Th1 to Th2 shift is unable to explain all the immunomodulatory effects of microbial infection that lead to prevention of T1D, and may instead require a more complex paradigm incorporating, for example, the action of Treg. HELMINTH MODULATION OF THE IMMUNE SYSTEM Amongst the various infectious agents, helminth parasites are regarded as master manipulators of the host immune 519 Figure 2 Immunoﬂuorescent staining of a NOD pancreas showing mononuclear cell inﬁltration. Section of NOD pancreas showing insulin producing β cell mass (orange) and mononuclear cells (green) stained with CD3. Pancreas from young mice show no inﬁltrate whereas (a) older mice show a spontaneous inﬁltration around the islet (b) initiating β cell destruction. © 2006 The Authors Journal compilation © 2006 Blackwell Publishing Ltd, Parasite Immunology, 28, 515–523