Atypical efferocytosis of live neutrophils dysregulates inflammation during P. gingivalis infection

Here, we show that neutrophils infected with the bacterial pathogen Porphyromonas gingivalis (Pg) are internalized alive by macrophages in a manner that bypasses all known efferocytic receptor-ligand interactions with highly inflammatory outcomes. Mechanistically, proteolytic cleavage of neutrophil granule proteins by the Pg protease RgpB generated non-canonical ligands that were recognized by macrophage aMb2 (CR3) receptors, facilitating the efferocytosis of live neutrophils. Contrary to the immunosuppression induced by apoptotic cells, efferocytosis of Pg-infected or RgpB-treated live neutrophils was highly inflammatory, with significant delays in efferosomal maturation. Thus, our data show a novel immune subversion strategy employed by a bacterial pathogen that utilizes a previously unknown receptor-ligand interaction for the efferocytosis of live cells and consequently dysregulates the resolution of inflammation.