The Effect of Chronic Helminth Infection on Type I Hypersensitivity
Abstract
IgE-mediated anaphylaxis is a life-threatening condition. Binding of IgE with its cognate antigen causes basophils and mast cells to rapidly release pre-formed inflammatory mediators. While numerous animal studies have reported that helminths can prevent allergic sensitization, only 4 studies to date have evaluated the effects of infection on pre-existing allergy. Since chronic helminth infection suppresses basophil and mast cell function, we hypothesized that chronic infection would protect against the immunological and clinical signs of anaphylaxis in previously sensitized mice. Briefly, mice were sensitized by intraperitoneal injection of either ovalbumin (OVA)/alum or PBS/alum once per week for 3 weeks. At 4 weeks, mice were infected with Litomosoides sigmodontis (L.s.), a rodent filarial parasite, or administered a mock treatment. Twelve weeks post-infection, immunological and clinical parameters were measured before and after allergic challenge with OVA. Following challenge, serum levels of murine mast cell protease-1 (mMCP-1) were significantly lower in sensitized mice that were L.s.-infected as compared to mock-treated. However, chronic infection with L. sigmodontis did not alter serum levels of OVA-IgE compared to mock infection. With respect to clinical signs, L.s.-infected mice that had been previously sensitized exhibited an average drop in core body temperature of 3.5C after 30 minutes, which was significantly less than the 5.0C drop observed in sensitized and mock-infected mice. Anaphylaxis was dependent on IgE-signaling, as FceRI knockout mice did not release mMCP-1 or exhibit a drop in core body temperature in response to intraperitoneal challenge with OVA. Further, anaphylaxis in our model was largely dependent on mast cells, with mast cell-deficient mice exhibiting a significantly impaired release of mMCP-1 and decrease in core body temperature compared to wild type- or basophil-depleted mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 18, 2018
- Accession Number
- AD1128435
Entities
People
- Laura E Kropp
Organizations
- Uniformed Services University of the Health Sciences