LPS promotes Th2 dependent sensitisation leading to anaphylaxis in a Pru p 3 mouse model

Maria J Rodriguez,Francisca Gomez,James R Perkins,Cristobalina Mayorga,Ana Aranda,Francisca Palomares,Tahia D Fernandez,Maria J Torres,Javier Rojo,Araceli Diaz-Perales,Nuria Cubells-Baeza

doi:10.1038/srep40449

Abstract

Pru p 3 is the major peach allergen in the Mediterranean area. It frequently elicits severe reactions, limiting its study in humans, raising the need for animal models to investigate the immunological mechanisms involved. However, no anaphylaxis model exists for Pru p 3. We aimed to develop a model of peach anaphylaxis by sensitising mice with Pru p 3 in combination with lipopolysaccharide (LPS) as an adjuvant. Four groups of mice were sensitised intranasally: untreated; treated with Pru p 3; treated with LPS; treated with Pru p 3 + LPS. After sensitisation mice were intraperitoneally challenged with Pru p 3 and in vivo and in vitro parameters were evaluated. Only mice in the Pru p 3 + LPS group showed anaphylaxis symptoms, including a decrease in temperature. Determination of in vitro parameters showed a Th2 response with an increase of Pru p 3-specific IgE and IgG1. Moreover, at the cellular level, we found increased levels of IgE and IgG1 secreting Pru p 3-specific cells and a proliferative CD4+ T-cell response. These results demonstrate that Pru p 3-specific anaphylaxis can be generated after nasal sensitisation to Pru p 3 in combination with LPS. This is a promising model for evaluating food allergy immunotherapies.

Highlights

Pru p 3 is the major peach allergen in the Mediterranean area
Symbols represent individual mice in each group: White circles for untreated group (N = 10); grey squares for Pru p 3 treated group (N = 10); grey triangles for LPS treated group (N = 10) and black squares for Pru p 3 plus LPS treated group (N = 10)
Mice sensitised with Pru p 3 +LPS, but not those sensitised with either Pru p 3 or LPS, developed systemic anaphylaxis (Fig. 2a), consisting of a significant decrease in body temperature (p = 0.0059) and appearance of severe clinical symptoms (Fig. 2b), demonstrated by inactivity, isolation and increased respiratory rate

Summary

Introduction

Pru p 3 is the major peach allergen in the Mediterranean area It frequently elicits severe reactions, limiting its study in humans, raising the need for animal models to investigate the immunological mechanisms involved. A small number of protein families contain allergens[3], one of the most important being lipid transfer proteins (LTP) from the Rosaceae family, which includes apple and peach Allergens from this family are frequently involved in allergic reactions to plant-derived foods[4,5]. The high sensitisation to Pru p 3, its cross-reactivity with other foods and pollens and its frequent involvement in severe reactions make it difficult to investigate the mechanisms underlying peach allergy in humans, several studies have been performed looking into the role of sIgE and its www.nature.com/scientificreports/. Statistical analysis were performed using the Wilcoxon test for related samples and significance was set at p < 0.05. (b) Clinical score, according to a scoring system: 0: no symptoms; 1: scratching and rubbing around the nose and head; 2: puffiness around the eyes and mouth, diarrhoea, ‘pilar erecti’, reduced activity and/

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