Murine Myeloid Progenitors Attenuate Immune Dysfunction Induced by Hemorrhagic Shock

Hemorrhagic shock induces an aberrant immune response characterized by simultaneous induction of a proinflammatory state and impaired host defenses. The objective of this study was to evaluate the impact of conditionally immortalized neutrophil progenitors (NPs) on this aberrant immune response. We employed a mouse model of hemorrhagic shock, followed by the adoptive transfer of NPs and subsequent inoculation of Staphylococcus aureus to induce pneumonia. We observed that transplant of NPs decreases the proportion of host neutrophils that express programmed death ligand 1 and intercellular adhesion molecule 1 in the context of prior hemorrhage. Following hemorrhage, NP transplant decreased proinflammatory cytokines in the lungs, increased neutrophil migration into the airspaces, and enhanced bacterial clearance. Further, hemorrhagic shock improved NP engraftment in the bone marrow. These results suggest that NPs hold the potential for use as a cellular therapy in the treatment and prevention of secondary infection following hemorrhagic shock. •Myeloid progenitors restore a competent inflammatory response to pneumonia•Progenitor transplantation promotes clearance of secondary S. aureus pneumonia•Hemorrhagic shock enhances engraftment of transplanted myeloid progenitors In this article, Cohen and colleagues evaluate the impact of myeloid progenitor transplantation in a “two-hit” mouse model of critical illness. The authors show that progenitor transplantation reverses a dysfunctional host response to secondary Staphylococcus aureus pneumonia induced by prior hemorrhagic shock.