Porphyromonas gingivalis Produce Neutrophil Specific Chemoattractants Including Short Chain Fatty Acids
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2020.620681/full |
| _version_ | 1818944209557651456 |
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| author | Agnes Dahlstrand Rudin Arsham Khamzeh Vignesh Venkatakrishnan Tishana Persson Michael Gabl Otto Savolainen Huamei Forsman Claes Dahlgren Karin Christenson Johan Bylund |
| author_facet | Agnes Dahlstrand Rudin Arsham Khamzeh Vignesh Venkatakrishnan Tishana Persson Michael Gabl Otto Savolainen Huamei Forsman Claes Dahlgren Karin Christenson Johan Bylund |
| author_sort | Agnes Dahlstrand Rudin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T07:39:35Z |
| format | Article |
| id | doaj.art-3fab8d504a6d4e3d8d51af1898f2fe37 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-20T07:39:35Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-3fab8d504a6d4e3d8d51af1898f2fe372022-12-21T19:48:10ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-01-011010.3389/fcimb.2020.620681620681Porphyromonas gingivalis Produce Neutrophil Specific Chemoattractants Including Short Chain Fatty AcidsAgnes Dahlstrand Rudin0Arsham Khamzeh1Vignesh Venkatakrishnan2Tishana Persson3Michael Gabl4Otto Savolainen5Huamei Forsman6Claes Dahlgren7Karin Christenson8Johan Bylund9Department of Oral Microbiology and Immunology, Institute of Odontology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenDepartment of Oral Microbiology and Immunology, Institute of Odontology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenDepartment of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenDepartment of Oral Microbiology and Immunology, Institute of Odontology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenDepartment of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenChalmers Mass Spectrometry Infrastructure, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, SwedenDepartment of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenDepartment of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenDepartment of Oral Microbiology and Immunology, Institute of Odontology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenDepartment of Oral Microbiology and Immunology, Institute of Odontology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenNeutrophil 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.https://www.frontiersin.org/articles/10.3389/fcimb.2020.620681/fullFFAR2GPR43granulocytepolymorphonuclear leucocyteperiodontitisacetate |
| spellingShingle | Agnes Dahlstrand Rudin Arsham Khamzeh Vignesh Venkatakrishnan Tishana Persson Michael Gabl Otto Savolainen Huamei Forsman Claes Dahlgren Karin Christenson Johan Bylund Porphyromonas gingivalis Produce Neutrophil Specific Chemoattractants Including Short Chain Fatty Acids Frontiers in Cellular and Infection Microbiology FFAR2 GPR43 granulocyte polymorphonuclear leucocyte periodontitis acetate |
| title | Porphyromonas gingivalis Produce Neutrophil Specific Chemoattractants Including Short Chain Fatty Acids |
| title_full | Porphyromonas gingivalis Produce Neutrophil Specific Chemoattractants Including Short Chain Fatty Acids |
| title_fullStr | Porphyromonas gingivalis Produce Neutrophil Specific Chemoattractants Including Short Chain Fatty Acids |
| title_full_unstemmed | Porphyromonas gingivalis Produce Neutrophil Specific Chemoattractants Including Short Chain Fatty Acids |
| title_short | Porphyromonas gingivalis Produce Neutrophil Specific Chemoattractants Including Short Chain Fatty Acids |
| title_sort | porphyromonas gingivalis produce neutrophil specific chemoattractants including short chain fatty acids |
| topic | FFAR2 GPR43 granulocyte polymorphonuclear leucocyte periodontitis acetate |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2020.620681/full |
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