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

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.

Pru p 3‐Epitope‐based sublingual immunotherapy in a murine model for the treatment of peach allergy

“…We confirmed the mice were anaphylactic after the 5 week sensitization period by performing an intraperitoneal challenge with Pru p 3, observing similar in vivo and in vitro data to those previously reported (data not shown). The in vivo evaluation showed that Sensitized, Treated with D 1 (Prup3)+CpG mice maintained a body temperature comparable to basal conditions and to that of the Non‐Sensitized group.…”

Transcriptional Profiling of Dendritic Cells in a Mouse Model of Food‐Antigen‐Induced Anaphylaxis Reveals the Upregulation of Multiple Immune‐Related Pathways

“…The lack of increase in Pru p 3‐specific IgE levels suggests the increased IgE is attached to cells, although further experiments will be needed to investigate this, as there is a clear tendency for increased levels in the anaphylactic animals. These findings are in line with previous studies using this model, however, other allergy models have found IgE secreting cell numbers to be less than IgG1 secreting cells, for example, in a murine model of allergic asthma . Pru p 3‐sIgG1 levels were also higher for anaphylactic animals versus Pru p‐3 only receiving animals; interestingly this is also in contrast with the antibody‐secreting cell numbers, which were higher for sIgE.…”

“…Female Balb/c mice aged 4–5 weeks (Janvier Lab, Saint‐Berthevin Cedex, France) were sensitized to peach using intranasally administered Pru p 3 in combination with LPS and challenged intraperitoneally as described previously . These will be referred to as anaphylactic mice.…”

“…To circumvent these constraints, we have performed in vivo studies by developing a mouse model of food‐antigen induced anaphylaxis, specifically peach‐anaphylaxis, that involves intranasal sensitization with peach extract and intraperitoneal allergen challenge. This model has also been used to test novel constructs for antigen‐specific immunotherapy .…”

Outstanding animal studies in allergy I. From asthma to food allergy and anaphylaxis

“…A recent study used peach allergen Pru p 3 with lipopolysaccharide as adjuvant for intranasal sensitization, and anaphylaxis could be elicited by intraperitoneal challenge [60]. The authors suggested this model to be suitable for testing immunotherapeutic strategies.…”