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The Use of Filariae as a Therapeutic Agent for Hypersensitivity Diseases

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Technical Report

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Uniformed Services University Of The Health Sciences Bethesda United States

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In this study we evaluated the effect chronic helminth infection has on allergic disease in mice previously sensitized to ovalbumin OVA. Ten weeks of infection with Litomosoides sigmodontis reduced immunological markers of type I hypersensitivity, including OVA-specific IgE, basophil activation, and mast cell degranulation. Despite these reductions, there was no protection against immediate clinical hypersensitivity as measured by changes in vascular permeability following intradermal OVA challenge. However, late phase ear swelling, due to type III hypersensitivity, was significantly reduced in chronically infected animals. Immune complexes visualized in the ear were slightly larger in the infected group. Levels of total IgG2a, OVA-specific IgG2a, and OVA-specific IgG1 were all reduced in the setting of infection. These reductions were likely due to increased antibody catabolism as ELISPOT assays demonstrated that infected animals do not have suppressed antibody production. Ear histology 24 hours after challenge showed infected animals have reduced cellular infiltration in the ear, with significant decreases in numbers of neutrophils and macrophages. Consistent with this finding, infected animals had significantly fewer neutrophil-specific chemokines CXCL1 and CXCL2 in the ear following challenge. Additionally, in vitro stimulation with immune-complexes resulted in significantly less CXCL1 and CXCL2 production by eosinophils from chronically infected mice. Expression of FcyRI was also significantly reduced on eosinophils from infected animals. Finally, we found that L. sigmodontis infection decreased anti-ds DNA autoantibodies and prevented mesangial expansion in mice with previously established systemic lupus erythematosus. These data indicate that chronic filarial infection suppresses eosinophilic responses to antibody-mediated activation and has the potential to be used as a therapeutic for pre-existing hypersensitivity diseases.

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