A single priming event prevents oral tolerance to peanut

Abstract

BackgroundIndoor 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.

Peanut butter feeding induces oral tolerance in genetically diverse collaborative cross mice

“…A modified oral tolerance model ( 24 ) was implemented, where mice were given peanut butter eight times before or during airway exposure to peanut plus LPS and assessed for sensitization and anaphylaxis to peanut as a readout of allergy ( Figure 1A ). Peanut consumption was monitored during ad libitum feeding; C57BL/6J and all CC strains consumed peanut, with an average consumption of ∼450 mg of peanut protein per feeding ( Figure 1B ).…”

“…Male CC ( n = 3–4 per strain) and C57BL/6J mice ( n = 8–10) between 5 and 14 weeks of age were used for experiments. The group sizes were based on power calculations from an earlier study ( 24 ) using male and female C57BL/6J mice and allowed for simultaneous screening of several CC strains. All animal experiments were approved by the Institutional Animal Care and Use Committee at the University of North Carolina at Chapel Hill.…”

“…To test oral tolerance in CC strains, we modified a LEAP mouse model ( 26 ) as previously described ( 24 ). Briefly, mice were given peanut butter (PB) bites ad libitum for 24 h on days -12, -10, -8, and -1, before the sensitization protocol and on days 2, 5, 9, and 12, during sensitization, as shown in Figure 1A .…”