Parasitic worms and inflammatory diseases

Abstract

The debate on whether infection precipitates or prevents autoimmunity remains a contentious one. Recently the suggestion that some unknown microbe can be at the origin of some chronic inflammatory diseases has been countered by accumulating evidence that decreasing infection rates might have an important role to play in the rising prevalence of autoimmune disorders. The 'Hygiene Hypothesis' was initially postulated to explain the inverse correlation between the incidence of infections and the rise of allergic diseases, particularly in the developed world. Latterly, the Hygiene Hypothesis has been extended to also incorporate autoimmune diseases in general. Amongst the various infectious agents, a particular emphasis has been put on the interaction between parasitic worms and humans. Worm parasites have co-evolved with the mammalian immune system for many millions of years and during this time, they have developed extremely effective strategies to modulate and evade host defences and so maintain their evolutionary fitness. It is therefore reasonable to conclude that the human immune system has been shaped by its relationship with parasitic worms and this may be a necessary requirement for maintaining our immunological health. Fully understanding this relationship may lead to novel and effective treatments for a host of deleterious inflammatory reactions.

Figure 1

Inverse correlation between Type 1 Diabetes (T1D) and ‘neglected infectious diseases’. Red delineates areas which harbour six or more of the low mortality neglected diseases (filariasis, leprosy, onchocerciasis, schistosomiasis, soil-transmitted helminths, and trachoma). Yellow delineates areas where there are relatively high incidences of T1D (> 8 per 100 000/year). Non coloured areas delineate where T1D < 8 per 100 000/year and where the ‘neglected diseases’ are not endemic.

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.

Figure 3

S. mansoni modulation of the immune response. S. mansoni live helminth and antigens modify cells of the innate immune system through interaction with TLRs and CLRs arresting the production inflammatory mediators and eliciting instead, the release of immunoregulatory cytokines such as IL-10. This results in the generation of suppressive Treg and a bias towards a Th2 response. aaMΦ; alternately activated macrophage.