In recent years, good experimental data has been provided to show that host regulatory pathways are activated by certain GI parasites in particular helminths. For example, the duodenal-dwelling nematode Heligmosomoides polygyrus can inhibit gut inflammation in the mouse associated with Helicobacter colitis [48], genetic IL-10 deficiency [49] or peanut allergy [50]; the same parasite stimulates Treg expansion and induction in vivo and in vitro[51–53]. In Trichuris muris infections of the colon, Tregs are required to minimize intestinal pathology and the parasite strain able to survive longest in the mouse is associated with the largest numerical expansion in Tregs[54]. Although

data from

human helminth infections are not so definitive, new and remarkable evidence has been provided for the presence of GI helminth-associated Tregs. A cohort of multiple sclerosis patients were selleck chemicals found to have acquired Selleckchem Roscovitine gut helminth infections while under longitudinal monitoring in the clinic; infected individuals showed a dramatically lower rate of relapse, with milder clinical scores, than case–controlled uninfected patients. Infected subjects showed higher correlates of Treg activity and lower inflammatory cytokine production on autoantigen stimulation, linking the helminth infection with expanded Treg activity and improved clinical outcome [55]. Studies to date have not been defined whether the Treg subsets stimulated by GI helminths are natural or induced, or if there are parasite-specific Treg populations among them. In addition, the relative importance of Tr1 (non-FoxP3-expressing, IL-10-producing) regulatory cells is brought into question by the dispensible nature of IL-10 for many

helminth-associated regulatory effects (for example [56]). By contrast, new data are clearly demonstrating an inherent capacity to promote induced Treg development and function in the Orotidine 5′-phosphate decarboxylase case of H. polygyrus secretions which drive de novo expression of FoxP3 in naive peripheral T cells. The distinction between Tregs and inducible regulatory T cells in vivo is not always clear, particularly in highly inflammatory settings. Moreover, Tregs may be able to influence the emergence or function of one another. This notion was suggested recently in a model of Aspergillus conidia infection in mice. In this model, control of allergic immunopathology induced by the fungus required the sequential activity of various populations of Tregs[57]. This sequential role for various populations of Tregs may not be an exception but rather the rule, as most infections proceed through various stages and therefore require various layers of regulation. The host, on the other hand, has many mechanisms which may uphold or restore responsiveness in a counter-regulatory fashion.