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Evaluation of Allergy Effector Cell Function: Suppression of Basophils in Chronic Helminth Infections

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Technical Report

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Uniformed Services University Of The Health Sciences Bethesda United States

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For the past several decades, allergic diseases have been increasing in industrialized countries. While the reasons for this increase are most likely multifold, both epidemiological and animal studies indicate that helminth infection suppresses atopy. The mechanisms by which helminth infection decrease allergic disease are currently unknown. The purpose of this thesis research was to determine whether helminth infection resulted in suppression of basophils, a well described allergy effector cell. To accomplish this, initial experiments were performed to determine whether basophil responsiveness was reduced in Litomosoides sigmodontis and Schistosoma mansoni rodent helminth infection models by assessing basophil intracellular IL-4 and surface CD200R levels after IgE-mediated stimulation using flow cytometry. Reduced basophil responsiveness developed in mice with chronic helminth infections. The mechanism responsible for basophil suppression was determined to be increased production of the anti-inflammatory cytokine IL-10 during infection. Basophil responsiveness returned to baseline uninfected levels after helminths were no longer present. Additional experiments measuring histamine release from blood basophils of uninfected humans and humans with intestinal helminth infections were performed after anti-IgE and ionomycin stimulation. Basophils from uninfected humans released more histamine than basophils from infected humans. Additionally, basophils from infected children released more histamine 2 weeks after anthelmintic treatment. Together, these data indicate that reduced basophil functionality develops during helminth infection and requires the presence of live helminths. Reduced basophil functionality could have broad medical implications. Not only are basophils effector cells of allergy, but studies demonstrate that basophils play prominent roles in the development of type 2 immune responses, the type of immune response that drives allergic disease.

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