Porphyromonas gingivalis Produce Neutrophil Specific Chemoattractants Including Short Chain Fatty Acids
Journal article, 2021

Neutrophil migration from blood to tissue-residing microbes is governed by a series of chemoattractant gradients of both endogenous and microbial origin. Periodontal disease is characterized by neutrophil accumulation in the gingival pocket, recruited by the subgingival biofilm consisting mainly of gram-negative, anaerobic and proteolytic species such as Porphyromonas gingivalis. The fact that neutrophils are the dominating cell type in the gingival pocket suggests that neutrophil-specific chemoattractants are released by subgingival bacteria, but characterization of chemoattractants released by subgingival biofilm species remains incomplete. In the present study we characterized small (< 3 kDa) soluble chemoattractants released by growing P. gingivalis, and show that these are selective for neutrophils. Most neutrophil chemoattractant receptors are expressed also by mononuclear phagocytes, the free fatty acid receptor 2 (FFAR2) being an exception. In agreement with the selective neutrophil recruitment, the chemotactic activity found in P. gingivalis supernatants was mediated in part by a mixture of short chain fatty acids (SCFAs) that are recognized by FFAR2, and other leukocytes (including monocytes) did not respond to SCFA stimulation. Although SCFAs, produced by bacterial fermentation of dietary fiber in the gut, has previously been shown to utilize FFAR2, our data demonstrate that the pronounced proteolytic metabolism employed by P. gingivalis (and likely also other subgingival biofilm bacteria associated with periodontal diseases) may result in the generation of SCFAs that attract neutrophils to the gingival pocket. This finding highlights the interaction between SCFAs and FFAR2 in the context of P. gingivalis colonization during periodontal disease, but may also have implications for other inflammatory pathologies involving proteolytic bacteria.

periodontitis

polymorphonuclear leucocyte

short chain fatty acid

granulocyte

FFAR2

acetate

GPR43

propionate

Author

Agnes Dahlstrand Rudin

University of Gothenburg

Arsham Khamzeh

University of Gothenburg

Vignesh Venkatakrishnan

University of Gothenburg

Tishana Persson

University of Gothenburg

Michael Gabl

University of Gothenburg

Otto Savolainen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Huamei Forsman

University of Gothenburg

Claes Dahlgren

University of Gothenburg

Karin Christenson

University of Gothenburg

Johan Bylund

University of Gothenburg

Frontiers in cellular and infection microbiology

22352988 (eISSN)

Vol. 10 620681

Subject Categories

Pharmacology and Toxicology

Microbiology

Microbiology in the medical area

DOI

10.3389/fcimb.2020.620681

PubMed

33542906

More information

Latest update

4/1/2022 7