The effectiveness of hematopoietic stem cell transplantation as a therapy is complicated by pulmonary infections. Using our syngeneic bone marrow transplant (BMT) mouse model, BMT mice displayed increased susceptibility to Pseudomonas aeruginosa and Staphylococcus aureus. BMT alveolar macrophages (AMs) exhibited a defect in P. aeruginosa phagocytosis while S. aureus uptake was enhanced. This difference was due to an altered scavenger receptor (SR) profile. Interestingly, MARCO expression was decreased while SR-AI/II was increased. Phagocytosis assays with SR-AI/II transfected-CHO cells revealed SR-AI/II was important for S. aureus uptake but not P. aeruginosa. Conversely, AMs treated in vitro with soluble MARCO exhibited similar defects in P. aeruginosa internalization as did BMT AMs. miR-155 targets the 3’UTR of SR-AI, however, its expression is decreased post-BMT. Anti-miR-155-transfected AMs exhibited an increase in SR-AI/II expression and S. aureus phagocytosis. In vitro treatment of AMs with prostaglandin E2 (PGE2) (elevated post-BMT) increased SR-AI/II, and decreased MARCO and miR-155. Despite a difference in phagocytosis, BMT AMs harbor a killing defect to both P. aeruginosa and S. aureus. Thus, our data suggest that PGE2-driven alterations in SR and miR-155 expression account for the differential phagocytosis of P. aeruginosa and S. aureus but impaired killing ultimately confers increased susceptibility to pulmonary infection.
- Copyright © 2013 by The American Association of Immunologists, Inc.