Helminth infection favors persistent and proliferating alternatively activated neutrophils in the lung 2684

Abstract Description Neutrophils are granulocytic myeloid cells that have critical effector functions during infectious disease but are typically thought to be short-lived, terminally differentiated phagocytic cells. We directly compared lung neutrophil activation following infection with different groups of pathogens including bacteria (Staphylococcus aureus), fungi (Aspergillus fumigatus), and helminths (Nippostrongylus brasiliensis) at 2 days after infection. Our results showed considerable heterogeneity depending on the type of infectious agent. Bulk RNAseq, EdU incorporation, and flow cytometric staining for necrosis/apoptosis identified distinct activation states with rapid cell death predominant in neutrophils after S. aureus and A. fumigatus infection, while neutrophils from helminth infected mice exhibited increased cell cycling and expression of signaling pathways associated with proliferation, type 2 responses, and wound healing. Spectral flow cytometry, intravascular staining, and scRNAseq revealed a distinct c-kit+ proliferating subset of lung neutrophils that expanded shortly after helminth infection and was released from the endothelial niche to co-localize with invading parasites in the airways. These findings challenge current models of neutrophil function during infectious disease, suggesting that neutrophils uniquely assume a persistent and proliferative phenotype that may contribute to tissue repair and resistance in the context of the type 2 pulmonary inflammatory response. Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)