Proteomics

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


ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Primary Cell, Neutrophil

SUBMITTER: Luiz Gustavo de Almeida  

LAB HEAD: Dr. Antoine Dufour

PROVIDER: PXD051073 | Pride | 2025-07-14

REPOSITORIES: Pride

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Publications


Neutrophils are highly abundant in the oral mucosal tissues, and their balanced activation and clearance are essential for immune homeostasis. Here, we demonstrate that neutrophils infected with the bacterial pathogen Porphyromonas gingivalis (Pg) are captured alive by macrophages in a manner that bypasses all known receptor-ligand interactions involved in the phagocytosis of either live or dead cells. Mechanistically, upon interaction with Pg, or its protease RgpB (gingipains), live neutrophils  ...[more]

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