Schistosoma mansoni modulation of allergic responses

THESIS 7920It has been proposed that in humans infection with certain parasitic helminths may reduce the propensity to develop allergies in infected populations. Schistosoma mansoni is a parasitic trematode that is implicated as a reducer of allergic responses in humans. The association between helminths and allergies is intrinsic to the as yet inadequately tested Hygiene Hypothesis. In this PhD I have used mouse models of allergies to formally experimentally test the role of Schistosoma m ansoni in the Hygiene Hypothesis. I demonstrate that while mice with conventional S. mansoni egg-producing infections are partially resistant to anaphylaxis, they are predisposed to developing exacerbated spontaneous and allergen-induced pulmonary inflammation including airway hyperresponsiveness. In contrast, I now demonstrate that mice infected with only schistosome worms are refractory to both anaphylaxis and allergen-induced airway hyperresponsiveness. I have dissected the underlying immunological mechanisms that mediate the resistance of worm-infected mice to both allergic insults. I propose a new paradigm whereby schistosome worms are resistant to allergic pulmonary inflammation via what I have term ed a "helminth-modified pulmonary type 2 response". In this paradigm schistosome worms suppress allergen-induced interleukin-5 which leads to lower pulmonary eosinophilia and normal lung function. Additionally, I have shown that the regulatory cytokine IL-10 is essential to mediate resistance of worm-infected mice to allergic disease. At the cellular level I show a new role for B cells and CD1d+ cells in resistance to anaphylaxis and AHR