The Effect of the Food Matrix on In Vivo Immune Responses to Purified Peanut Allergens

Abstract

There is little knowledge about the factors that determine the allergenicity of food proteins. One aspect that remains to be elucidated is the effect of the food matrix on immune responses to food proteins. To study the intrinsic immunogenicity of allergens and the influence of the food matrix, purified peanut allergens (Ara h 1, Ara h 2, Ara h 3, or Ara h 6) and a whole peanut extract (PE) were tested in the popliteal lymph node assay (PLNA) and in an oral model of peanut hypersensitivity. In the PLNA, peanut proteins were injected into the hind footpad of BALB/c mice; in the oral exposure experiments C3H/HeOuJ mice were gavaged weekly with PE or allergens in the presence of cholera toxin (CT). Upon footpad injection, none of the allergens induced significant immune activation. In contrast, PE induced an increase in cell number, cytokine production, and activation of antigen-presenting cells. Furthermore, the presence of a food matrix enhanced the immune response to the individual allergens. Oral exposure to the purified allergens in the presence of CT induced specific IgE responses, irrespective of the presence of a food matrix. These results suggest that purified peanut allergens possess little intrinsic immune-stimulating capacity in contrast to a whole PE. Moreover, the data indicate that the food matrix can influence responses to individual proteins and, therefore, the food matrix must be taken into account when developing models for allergenic potential assessment.

Peanut lipids display potential adjuvanticity by triggering a pro‐inflammatory response in human keratinocytes

“…Our findings are in line with previous studies demonstrating that the matrix from allergen sources contains compounds that might aid allergic sensitization and lipids may play a fundamental role 1, 2, 3. The pro‐inflammatory mediators produced by KC upon PNL stimulation may perhaps lead to barrier disruption and promote the proper environment allowing Ara h 1 or Ara h 2 to penetrate the epidermis and recruit neighboring cells involved in the allergic sensitization process 6.…”

“…Exposure of infants to peanut oil‐containing lotions was described as a risk factor for the development of peanut allergy 1. There is evidence that only peanut extracts containing lipids were able to induce sensitization 2, 3. How this occurs at the molecular level is still unknown.…”

“…Such mediators were shown to cause barrier disruption, facilitate allergen penetration and initiate cutaneous inflammation 5, 6. Interestingly, allergens coadministered with PNL were not able to modify (neither inhibit nor synergize) this effect of PNL, suggesting that the capacity of PNL to activate the innate immune system is maintained in the presence of the allergens, as in crude peanut extract 2, 3. In contrast, peanut allergens coadministered with PNL inhibited the production of PNL‐induced IL‐10, likely produced by KC as a compensatory mechanism.…”

Induction of an antigen specific gut inflammatory reaction in mice and rats: a model for human Inflammatory Bowel Disease

“…Both IL-4 and IFN-γ production as well as IgE, IgG1 and IgG2a were found at the very early phase of the response to peanuts. The same group also examined the role of cytotoxic T-lymphocyte associated antigen 4 (CTLA-4), a negative regulator of T cell activation, on peanut sensitization (Van Wijk et al, 2005b). The use of an antibody against CTLA-4 in a murine model of peanut allergy failed to elicit an allergen-specific response.…”

Peanut Allergenicity and Cross-Reactivity with Pea Proteins in the In Vivo Model

“…It was clearly shown that C3H/HeJ mice can be used in studies on induced anaphylaxis (IgE-mediated) and that its clinical course (T-and B-cells responses) was similar to that occurring in individuals with hypersensitivity to peanuts [Li et al, 2000]. Also other species of mice: BALB/c, DBA/2, A/J, BDF-1, C57B/6, are used in studying the mechanisms of food allergy [Ladics et [Pramod et al, 2007;van Wijk et al 2005]. In our studies, BALB/c mice were used to determine their utility in studies related to food reaction caused by peanut protein administration (crude extract).…”