Bacterial skin infection primes bone marrow eosinophils to promote allergic skin-lung crosstalk
Microbial exposure at barrier interfaces drives development and balance of the immune system, but the consequences of local infections for systemic immunity and secondary inflammation are unclear. Here, we show that dermal exposure to the bacterium Staphylococcus aureus persistently shapes the immune system of mice with specific impact on progenitor and mature bone marrow neutrophil and eosinophil populations. The infection-imposed changes in eosinophils were long-lasting with functional changes associated with epigenetic and metabolic reprogramming, indicative of trained immunity. Bacterial exposure enhanced dermal allergic sensitization and resulted in exacerbated allergen-induced lung inflammation. S. aureus-mediated reprogramming of bone marrow eosinophils was driven by the alarmin interleukin 33 and the complement cleavage fragment C5a. Our study highlights the systemic impact of skin inflammation and reveals eosinophil progenitor training and organ-crosstalk mechanisms that modulate systemic responses to allergens. Overall design: Bone marrow-derived eosinophils were isolated from mice subjected to epicutaneous Staphylococcus aureus skin infection. ATAC-seq analysis was performed to assess changes in chromatin accessibility and epigenetic reprogramming. Differentially accessible regions were associated with immune memory and inflammatory pathways, contributing to the understanding of systemic immune training and eosinophil function.