Indoor dust acts as an adjuvant to promote sensitization to peanut through the airway

Abstract

Background There is growing evidence that environmental peanut exposure through non‐oral routes, including the skin and respiratory tract, can result in peanut sensitization. Environmental adjuvants in indoor dust can promote sensitization to inhaled antigens, but whether they contribute to peanut allergy development is unclear. Objective We investigated whether indoor dust promotes airway sensitization to peanut and peanut allergy development in mice. Methods Female and male C57BL/6J mice were exposed via the airways to peanut, indoor dust extract, or both for 2 weeks. Mice were then challenged with peanut and assessed for anaphylaxis. Peanut‐specific immunoglobulins, peanut uptake by lung conventional dendritic cells (cDCs), lung innate cytokines, and T cell differentiation in lung‐draining lymph nodes were quantified. Innate cytokine production by primary human bronchial epithelial cells exposed to indoor dust was also determined. Results Inhalational exposure to low levels of peanut in combination with indoor dust, but neither alone, resulted in production of peanut‐specific IgE and development of anaphylaxis upon peanut challenge. Indoor dust triggered production of innate cytokines in murine lungs and in primary human bronchial epithelial cells. Additionally, inhaled indoor dust stimulated maturation and migration of peanut‐laden lung type 1 cDCs to draining lymph nodes. Inhalational exposure to peanut and indoor dust induced peanut‐specific T helper 2 cell differentiation and accumulation of T follicular helper cells in draining lymph nodes, which were associated with increased B cell numbers and peanut‐specific immunoglobulin production. Conclusions & clinical relevance Indoor dust promotes airway sensitization to peanut and development of peanut allergy in mice. Our findings suggest that environmental adjuvants in indoor dust may be determinants of peanut allergy development in children.

Developmental Origins of Health and Disease: Impact of environmental dust exposure in modulating microbiome and its association with non-communicable diseases

“…108 Smeekens et al have demonstrated an adjuvant effect of house dust, which enhanced peanut sensitization and ensuing peanut allergy in mice. 109 A study by Ormstad et al demonstrated that indoor SPM, particularly those less than 2.5 μm in diameter, acts as an allergen carrier and adjuvant capable of modulating local lymph node inflammatory responses. 110 It was suggested that the fine particles (PM 2.5 fraction) were able to penetrate deeply into the airways, inducing epithelial irritability and increased sensitivity to environmental allergens, which subsequently affect respiratory health and induce the chronic airway inflammation characteristic of asthma.…”

Recent advances in mechanisms of food allergy and anaphylaxis

“…Experimental analyses also suggest that inhalation of food allergens can promote food sensitization and reactions 85 , 86 . Dolence et al .…”

“…Interestingly, a recent study revealed that indoor dust may act as an adjuvant and play a role in the exacerbation of inhaled food allergen sensitization. Inhaled indoor dust was shown to stimulate airway epithelial innate cytokine production and maturation, and lung type-1 cDCs and co-exposure of indoor dust and food allergens such as peanut led to the development of peanut‐specific Th2 cell differentiation and the accumulation of Tfh cell peanut‐specific IgE production 85 .…”

The uncertainties and anxieties around food allergy

“…Finally, Smeekens et al have looked at whether indoor dust promotes airway sensitization to peanut and peanut allergy development in mice, as they do for aeroallergens . In this model, inhalation of low levels of peanut only caused peanut allergy when combined with indoor dust (Figure ).…”