Single-Cell RNA sequencing of hematopoietic and non-hematopoietic cells defines a distinct signature in atopic and NRG1 mouse lung

Both treatments reduced alveolar macrophages, lymphatic endothelial cells, airway smooth muscle cells, and pericytes, while increasing alveolar type 2 cells. However, atopy led to increased fibroblasts and megakaryocytes with reduced club cells compared to NRG1 treatment. Further, in the hematopoietic cell compartment, atopy drove an increase in more inflammatory cells than NRG1 and associated with significant upregulation of immune cell signaling pathways, something not seen with NRG1 administration.

Moreover, NRG1 knockdown did not reverse the protection from virus-induced death in mice with pre-existing atopy. Taken together, these data strongly suggest that atopy and NRG1 mediate increased survival from a respiratory viral infection through disparate mechanisms.