Coating and corruption of human neutrophils by bacterial outer membrane vesicles

Porphyromonas gingivalis is a keystone oral pathogen that successfully manipulates the human innate immune defenses, resulting in a chronic pro-inflammatory state of periodontal tissues and beyond. Here we demonstrate that secreted outer membrane vesicles (OMVs) are deployed by P. gingivalis to selectively coat and activate human neutrophils, thereby provoking degranulation without neutrophil killing. Secreted granule components with antibacterial activity, especially LL-37 and MPO, are subsequently degraded by potent OMV-bound proteases known as gingipains, thereby ensuring bacterial survival. In contrast to neutrophils, the P. gingivalis OMVs are efficiently internalized by macrophages and epithelial cells. Importantly, we show that neutrophil coating is a conserved feature displayed by OMVs of at least one other oral pathogen, namely Aggregatibacter actinomycetemcomitans. Altogether, we conclude that P. gingivalis deploys its OMVs for a neutrophil-deceptive strategy to escape phagocytosis and to create a favorable inflammatory niche.