Neutrophil progenitor cell therapy rescues host defense against <i>Staphylococcus aureus</i> in murine chronic granulomatous disease

Despite advances in engineered adaptive immune cell therapies, current options for innate immune cell therapies are sparse. In this work, we demonstrate the utility of a neutrophil progenitor (NP)-based cell therapy. Murine conditionally immortalized NPs overcome some of the hurdles of alternative cell therapies, such as granulocyte transfusion, by engrafting in the unconditioned host and undergoing substantial expansion in vivo. Here, we demonstrate the therapeutic value of NPs using a murine model of the primary immunodeficiency chronic granulomatous disease (CGD). Those with CGD are highly susceptible to infection with Staphylococcus aureus because of genetic mutations that impair neutrophil antimicrobial function. We find that the prophylactic treatment of CGD mice with transfused NPs rescues them from an otherwise lethal S. aureus pulmonary infection. In investigating the mechanisms behind the improved clearance of S. aureus and survival of CGD mice, our data suggest that the antimicrobial function of host CGD neutrophils is rescued by the presence of donor-derived wild-type neutrophils. We also observe that survival is improved to >50% in the CGD model when mice receive NPs postinfection. This work highlights the application of NPs to improving outcomes to acute bacterial infection in CGD, demonstrating the translational potential of conditionally immortalized myeloid progenitors as a cellular therapy.