Farm dust primes macrophages to protect against allergic asthma

Allergic asthma is one of the most common chronic disease in children, and can also prevail into adulthood. Several independent studies found that growing up in a rural environment has a protective effect on children, reducing their risk of developing allergies and allergic asthma. A concerted effort has been made to elucidate the underlying cause of this protective effect, but the role of macrophages has not been fully understood and thus requires further investigation. We hypothesize that repeated exposure to a farm environment primes the innate immune system, specifically macrophages, decreasing their response towards allergens. In a murine ovalbumin (OVA) induced allergic asthma model, repeated intranasal application of farm dust during the sensitization phase significantly reduced airway hyper responsiveness (Rn at 24mg/ml methacholine from 2.5 to 1.8) and eosinophil number (90% reduction) in bronchoalveolar lavage fluid and OVA specific IgE (112 to 9.9ng/ml) in serum. Immunohistochemistry and flow cytometry showed an increase in macrophage numbers in the lung upon farm dust treatment. Single-cell RNA sequencing revealed shifts in the prevalence of lung-resident macrophages and monocyte-derived macrophages. To investigate molecular changes, we carried out ex-vivo experiments with murine bone marrow derived macrophages (BMDMs) and performed bulk RNA and ATAC sequencing. Repeated treatment with farm dust primed BMDMs, reducing their response to a secondary stimulation with LPS or IL-4. The exact mechanism by which farm dust primes macrophages needs further investigation. However, we found potential pathways which could explain our initial findings.