ICAM-1 expressed on neutrophils is critically involved in vaccine-induced protection in a murine model of acute pneumonia (97.3)

Abstract

Abstract Murine neutrophils are not known to express ICAM-1. In studying the mechanism of protection against P. aeruginosa pneumonia following immunization with a live-attenuated vaccine in a model of acute pneumonia, we detected ICAM-1 expression on lung neutrophils after challenge. We hypothesized that neutrophil ICAM-1 elicited homotypic adhesion as well as enhanced bacterial killing. C3H/HeN mice immunized intranasally (IN) with an aroA deletion mutant of P. aeruginosa strain PAO1 (PAO1ΔaroA) or E. coli (as control) at weekly intervals with 108, 5 x 108, and 109 CFU were challenged IN 3 weeks later with a cytotoxic variant of PAO1. Lung leukocytes and BAL cells were analyzed by flow cytometry, and decreased migration due to homotypic adhesion was assessed using Transwells. We also tested the impact of ICAM-1 blockade on bacterial clearance by IN instillation of anti-ICAM-1 antibody prior to challenge of immunized mice. PAO1ΔaroA-immune mice had more ICAM-1+ neutrophils in BAL 18 h after challenge compared with E. coli-immune controls (mean 74% vs. 37%, p < 0.01). Non-immune mice had low levels of ICAM-1+ neutrophils. BAL neutrophils from PAO1ΔaroA-immune mice transmigrated significantly less well, and blockade of ICAM-1 prior to challenge increased bacterial CFU in PAO1ΔaroA-immune mice. These data suggest that vaccine-induced neutrophil ICAM-1 plays an important role in the adaptive immune response in the lung.