Aversão e preferência ao sabor: mecanismos de proteção e dessensibilização na alergia alimentar ao amendoim

Abstract

Aversion to the allergenic food expresses an anxiety-like behavior, through which contact with the antigen is avoided to avoid the consequences of the allergic immune response. This phenomenon begins with the binding of the antigen to IgE-bound mast cells, which degranulate and release leukotrienes capable of inducing the production of GDF-15, a cytokine that indirectly activates the central nucleus of amygdala in the brain. Aversion is well described in the experimental model of allergy to ovalbumin (OVA), but it is still unclear whether this phenomenon occurs in other food allergies. Considering the clinical and epidemiological importance of peanut allergy, this study aimed to investigate food aversion in an experimental model of peanut allergy, as well as the immunological consequences of different levels of aversion in sensitized mice. In a preference test immediately after being sensitized with peanut protein extract (PPE), BALB/c and C57BL/6 mice preferred to ingest 3% whole peanut extract (3% WPE) than water, despite mast cell activation. However, after being challenged exclusively with 3% ETA for fourteen days, BALB/c, but not C57BL/6 mice, began to show aversion to 3% ETA in a preference test. This aversion coincided with higher serum levels of total IgE, anti-EPA IgE, MCPT-1, and GDF-15, as well as greater activation of the central nucleus of the amygdala. The aversion was reversed by increasing the ETA concentration from 3% to 10%, demonstrating that, in this context, aversion can be malleable due to an increase in the hedonic value of the antigenic solution. Based on these data, we tested the hypothesis that, in a context of low aversion, there is chronic exposure to the antigen that leads to a desensitization process. BALB/c mice were sensitized with OVA or Ara h 1, a major peanut allergen. During three weeks of oral challenge, half of the animals in each group could choose between drinking water or the antigenic solution: 20% egg white solution with 8% sucrose (20% SCO) or 10% ETA, respectively. The other half only had the option of drinking the antigenic solution. In the egg allergy group, when water was available, the sensitized mice rejected the 20% SCO and were therefore protected from inflammation. However, unlike the other group, the mice did not show a decrease in anti-OVA IgE production (desensitization) and had a more severe cutaneous anaphylactic reaction when challenged. On the other hand, the presence of water did not prevent the mice sensitized to Ara h 1 from ingesting the solution containing 10% ETA, despite the inflammation. Ultimately, both groups showed a decrease in anti-Ara h 1 IgE production. However, only the group that ingested exclusively ETA 10% presented a mild cutaneous anaphylactic reaction when challenged. Thus, mice sensitized to peanut antigens exhibit a malleable aversion despite mast cell activation, and choose to keep peanut in their diet in the long term, which might eventually lead to desensitization.