Bacterial skin infection imprints bone marrow eosinophils to promote allergic skin-lung crosstalk [Quant_seq]
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 epicutaneous 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 and associated with functional as well as imprinted epigenetic and metabolic changes. Bacterial exposure enhanced skin allergic sensitization and resulted in exacerbated allergen-induced lung inflammation. S. aureus-mediated functional bone marrow eosinophil reprogramming and pulmonary allergen responses were 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: To investigate the impact of local Staphylococcus aureus (SA) skin infection or PBS on bone marrow eosinophils and eosinophil progenitors, we performed bulk RNA-seq on those two sorted cell populations at day 7 post infection in 9-week old C57BL/6J mice (n=6).