NONOPSONIC PHAGOCYTOSIS OF PSEUDOMONAS-AERUGINOSA REQUIRES FACILITATED TRANSPORT OF D-GLUCOSE BY MACROPHAGES

Pseudomonas aeruginosa is the predominant respiratory tract pathogen i n patients with cystic fibrosis (CF), and its resistance to phagocytos is may contribute to its virulence. P. aeruginosa ingestion by macroph ages occurs only in the presence of D-glucose or D-mannose, sugars pre sent in low concentrations in the endobronchial space. Here we show th at only isolates of P. aeruginosa and not other bacterial species were ingested by murine macrophages in a glucose-dependent manner. Glucose transport inhibitors blocked both [H-3]-2-deoxy-glucose (2dG) uptake and phagocytosis of P. aeruginosa. P. aeruginosa pretreated with 2dG o r 5-thio-D-glucose (5TG) was efficiently ingested. Macrophages pretrea ted with 2dG or 5TG were able to bind but unable to ingest P. aerugino sa in the presence of glucose; however, they efficiently ingested zymo san or Igc-coated sheep erythrocytes. Macrophages produced lactate onl y from glucose or mannose. The facilitative glucose transporter GLUT1 mRNA transcript was detected by PCR in preparations from purified macr ophages. The nucleotide sequence of the PCR product was identical to t hat published for murine GLUT1. GLUT1 protein was detected with anti-G LUT1-peptide polyclonal Abs. We conclude that glucose exerts its effec t on the macrophage, not on the bacterium, in the glucose-dependent no nopsonic phagocytosis of P. aeruginosa and that glucose transport via GLUT1 by the macrophage is required to trigger ingestion. The unique g lucose dependency for phagocytosis of P. aeruginosa by macrophages may contribute to the pathogenicity of this bacterial species in CF patie nts.