A single priming event prevents oral tolerance to peanut

Abstract

AbstractBackgroundIndoor dust (ID) is a source of peanut proteins and immunostimulatory adjuvants (e.g. LPS) that can promote airway sensitization to peanut. We aimed to determine whether a single airway exposure to peanut plus adjuvant is sufficient to prevent oral tolerance.MethodsTo determine the effect of a single priming event, C57BL/6J mice were exposed once to peanut plus adjuvant through the airway, followed by either airway or low‐dose oral exposure to peanut, and assessed for peanut allergy. Oral tolerance was investigated by feeding high‐dose peanut followed by airway sensitization. To determine whether a single priming could prevent oral tolerance, the high‐dose peanut regimen was applied after a single airway exposure to peanut plus adjuvant. Peanut‐specific IgE and IgG1 were quantified, and mice were challenged to peanut to assess allergy. Peanut‐specific CD4+ memory T cells (CD4+TCRβ+CD44hiCD154+) were quantified in mediastinal lymph nodes following airway priming.ResultsMice co‐exposed to peanut with LPS or ID through the airway were primed to develop peanut allergy after subsequent low‐dose oral or airway exposures to peanut. Oral tolerance was induced in mice fed high‐dose peanut prior to airway sensitization. In contrast, mice fed high‐dose peanut following a single airway exposure to peanut plus adjuvant led to allergy. Peanut‐specific CD4+ memory T cells were detected as early as 7 days after the single airway priming with peanut plus adjuvant, however, delaying peanut feeding even 1 day following priming led to allergy, whereas peanut feeding the same day as priming led to tolerance.ConclusionsA single airway exposure to peanut plus adjuvant is sufficient to prime the immune system to develop allergy following subsequent high‐dose oral exposure. These results highlight the importance of introducing peanut as early as possible to prevent sensitization through a non‐oral priming event.