Mechanisms by which Porphyromonas gingivalis evades innate immunity
The oral cavity is home to unique resident microbial communities whose interactions with host immunity are less frequently studied than those of the intestinal microbiome. We examined the stimulatory capacity and the interactions of two oral bacteria, Porphyromonas gingivalis (P. gingivalis) and Fus...
| Main Authors: | , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2018
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| Online Access: | https://hdl.handle.net/10356/88032 http://hdl.handle.net/10220/44531 |
| _version_ | 1811684300110692352 |
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| author | Abdi, Kaveh Chen, Tsute Klein, Brian A. Tai, Albert K. Coursen, Jill Liu, Xiangdong Skinner, Jeff Periasamy, Saravanan Choi, Youngnim Kessler, Benedikt M. Palmer, Robert J. Gittis, Apostolos Matzinger, Polly Duncan, Margaret J. Singh, Nevil J. |
| author2 | Amar, Salomon |
| author_facet | Amar, Salomon Abdi, Kaveh Chen, Tsute Klein, Brian A. Tai, Albert K. Coursen, Jill Liu, Xiangdong Skinner, Jeff Periasamy, Saravanan Choi, Youngnim Kessler, Benedikt M. Palmer, Robert J. Gittis, Apostolos Matzinger, Polly Duncan, Margaret J. Singh, Nevil J. |
| author_sort | Abdi, Kaveh |
| collection | NTU |
| description | The oral cavity is home to unique resident microbial communities whose interactions with host immunity are less frequently studied than those of the intestinal microbiome. We examined the stimulatory capacity and the interactions of two oral bacteria, Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum), on Dendritic Cell (DC) activation, comparing them to the effects of the well-studied intestinal microbe Escherichia coli (E. coli). Unlike F. nucleatum and E. coli, P. gingivalis failed to activate DCs, and in fact silenced DC responses induced by F. nucleatum or E. coli. We identified a variant strain of P. gingivalis (W50) that lacked this immunomodulatory activity. Using biochemical approaches and whole genome sequencing to compare the two substrains, we found a point mutation in the hagA gene. This protein is though to be involved in the alteration of the PorSS/gingipain pathway, which regulates protein secretion into the extracellular environment. A proteomic comparison of the secreted products of the two substrains revealed enzymatic differences corresponding to this phenotype. We found that P. gingivalis secretes gingipain(s) that inactivate several key proinflammatory mediators made by DCs and/or T cells, but spare Interleukin-1 (IL-1) and GM-CSF, which can cause capillary leaks that serve as a source of the heme that P. gingivalis requires for its survival, and GM-CSF, which can cause epithelial-cell growth. Taken together, our results suggest that P. gingivalis has evolved potent mechanisms to modulate its virulence factors and dampen the innate immune response by selectively inactivating most proinflammatory cytokines. |
| first_indexed | 2024-10-01T04:26:26Z |
| format | Journal Article |
| id | ntu-10356/88032 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:26:26Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/880322020-09-21T11:33:13Z Mechanisms by which Porphyromonas gingivalis evades innate immunity Abdi, Kaveh Chen, Tsute Klein, Brian A. Tai, Albert K. Coursen, Jill Liu, Xiangdong Skinner, Jeff Periasamy, Saravanan Choi, Youngnim Kessler, Benedikt M. Palmer, Robert J. Gittis, Apostolos Matzinger, Polly Duncan, Margaret J. Singh, Nevil J. Amar, Salomon Singapore Centre for Environmental Life Sciences Engineering Porphyromonas Gingivalis Autacoid The oral cavity is home to unique resident microbial communities whose interactions with host immunity are less frequently studied than those of the intestinal microbiome. We examined the stimulatory capacity and the interactions of two oral bacteria, Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum), on Dendritic Cell (DC) activation, comparing them to the effects of the well-studied intestinal microbe Escherichia coli (E. coli). Unlike F. nucleatum and E. coli, P. gingivalis failed to activate DCs, and in fact silenced DC responses induced by F. nucleatum or E. coli. We identified a variant strain of P. gingivalis (W50) that lacked this immunomodulatory activity. Using biochemical approaches and whole genome sequencing to compare the two substrains, we found a point mutation in the hagA gene. This protein is though to be involved in the alteration of the PorSS/gingipain pathway, which regulates protein secretion into the extracellular environment. A proteomic comparison of the secreted products of the two substrains revealed enzymatic differences corresponding to this phenotype. We found that P. gingivalis secretes gingipain(s) that inactivate several key proinflammatory mediators made by DCs and/or T cells, but spare Interleukin-1 (IL-1) and GM-CSF, which can cause capillary leaks that serve as a source of the heme that P. gingivalis requires for its survival, and GM-CSF, which can cause epithelial-cell growth. Taken together, our results suggest that P. gingivalis has evolved potent mechanisms to modulate its virulence factors and dampen the innate immune response by selectively inactivating most proinflammatory cytokines. Published version 2018-03-09T04:48:03Z 2019-12-06T16:54:32Z 2018-03-09T04:48:03Z 2019-12-06T16:54:32Z 2017 Journal Article Abdi, K., Chen, T., Klein, B. A., Tai, A. K., Coursen, J., Liu, X., et al. (2017). Mechanisms by which Porphyromonas gingivalis evades innate immunity. PLOS One, 12(8), e0182164-. https://hdl.handle.net/10356/88032 http://hdl.handle.net/10220/44531 10.1371/journal.pone.0182164 en PLOS ONE © 2017 The Author(s) (Public Library of Science). This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. 20 p. application/pdf |
| spellingShingle | Porphyromonas Gingivalis Autacoid Abdi, Kaveh Chen, Tsute Klein, Brian A. Tai, Albert K. Coursen, Jill Liu, Xiangdong Skinner, Jeff Periasamy, Saravanan Choi, Youngnim Kessler, Benedikt M. Palmer, Robert J. Gittis, Apostolos Matzinger, Polly Duncan, Margaret J. Singh, Nevil J. Mechanisms by which Porphyromonas gingivalis evades innate immunity |
| title | Mechanisms by which Porphyromonas gingivalis evades innate immunity |
| title_full | Mechanisms by which Porphyromonas gingivalis evades innate immunity |
| title_fullStr | Mechanisms by which Porphyromonas gingivalis evades innate immunity |
| title_full_unstemmed | Mechanisms by which Porphyromonas gingivalis evades innate immunity |
| title_short | Mechanisms by which Porphyromonas gingivalis evades innate immunity |
| title_sort | mechanisms by which porphyromonas gingivalis evades innate immunity |
| topic | Porphyromonas Gingivalis Autacoid |
| url | https://hdl.handle.net/10356/88032 http://hdl.handle.net/10220/44531 |
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