Different airborne particulates trigger distinct immune pathways leading to peanut allergy in a mouse model

Background Environmental exposure to peanut through non‐oral routes is a risk factor for peanut allergy. Early‐life exposure to air pollutants, including particulate matter (PM), is associated with sensitization to foods through unknown mechanisms. We investigated whether PM promotes sensitization to environmental peanut and the development of peanut allergy in a mouse model. Methods C57BL/6J mice were co‐exposed to peanut and either urban particulate matter (UPM) or diesel exhaust particles (DEP) via the airways and assessed for peanut sensitization and development of anaphylaxis following peanut challenge. Peanut‐specific CD4+ T helper (Th) cell responses were characterized by flow cytometry and Th cytokine production. Mice lacking select innate immune signaling genes were used to study mechanisms of PM‐induced peanut allergy. Results Airway co‐exposure to peanut and either UPM‐ or DEP‐induced systemic sensitization to peanut and anaphylaxis following peanut challenge. Exposure to UPM or DEP triggered activation and migration of lung dendritic cells to draining lymph nodes and induction of peanut‐specific CD4+ Th cells. UPM‐ and DEP‐induced distinct Th responses, but both stimulated expansion of T follicular helper (Tfh) cells essential for peanut allergy development. MyD88 signaling was critical for UPM‐ and DEP‐induced peanut allergy, whereas TLR4 signaling was dispensable. DEP‐induced peanut allergy and Tfh‐cell differentiation depended on IL‐1 but not IL‐33 signaling, whereas neither cytokine alone was necessary for UPM‐mediated sensitization. Conclusion Environmental co‐exposure to peanut and PM induces peanut‐specific Tfh cells and peanut allergy in mice. We used an animal model to explore the mechanisms by which particulate matter (PM) exposure promotes food sensitization. Environmental co‐exposure to peanut and PM induced peanut‐specific Tfh cells, leading to peanut sensitization and allergy in mice. Different types of PM induced peanut sensitization through distinct innate immune pathways.Abbreviations: DEP, Diesel exhaust particles; IgE, Immunoglobulin E; Myd88, Myeloid differentiation primary response 88; PM, Particulate matter; Tfh, T follicular helper.