Nigericin Promotes NLRP3-Independent Bacterial Killing in Macrophages
Altered microbiota has been associated with a number of diseases, including inflammatory bowel diseases, diabetes, and cancer. This dysregulation is thought to relate the host inflammatory response to enteric pathogens. Macrophages play a key role in host response to microbes and are involved in bac...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02296/full |
| _version_ | 1819195550094852096 |
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| author | Heather Armstrong Heather Armstrong Michael Bording-Jorgensen Michael Bording-Jorgensen Richard Chan Richard Chan Eytan Wine Eytan Wine Eytan Wine |
| author_facet | Heather Armstrong Heather Armstrong Michael Bording-Jorgensen Michael Bording-Jorgensen Richard Chan Richard Chan Eytan Wine Eytan Wine Eytan Wine |
| author_sort | Heather Armstrong |
| collection | DOAJ |
| description | Altered microbiota has been associated with a number of diseases, including inflammatory bowel diseases, diabetes, and cancer. This dysregulation is thought to relate the host inflammatory response to enteric pathogens. Macrophages play a key role in host response to microbes and are involved in bacterial killing and clearance. This process is partially mediated through the potassium efflux-dependent, cytosolic, PYCARD-containing inflammasome protein complex. Surprisingly, we discovered an alternative mechanism for bacterial killing, independent of the NLRP3 inflammasome/PYCARD. Using the NLRP3 inflammasome-deficient Raw 264.7 and PYCARD-deficient J77 macrophages, which both lack PYCARD, we found that the potassium efflux activator nigericin enhances bacterial killing. Macrophage response to nigericin was examined by RT gene profiling and subsequent qPCR, which demonstrated altered expression of a series of genes involved in the IL-18 bacterial killing pathway. Based on our results we propose a model of bacterial killing, unrelated to NLRP3 inflammasome activation in macrophage cells. Improving understanding of the molecular pathways driving bacterial clearance within macrophage cells will aid in the development of novel immune-targeted therapeutics in a number of diseases. |
| first_indexed | 2024-12-23T02:14:32Z |
| format | Article |
| id | doaj.art-189abe35f4d246c09a86e2800cfc6373 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T02:14:32Z |
| publishDate | 2019-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-189abe35f4d246c09a86e2800cfc63732022-12-21T18:03:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-10-011010.3389/fimmu.2019.02296442332Nigericin Promotes NLRP3-Independent Bacterial Killing in MacrophagesHeather Armstrong0Heather Armstrong1Michael Bording-Jorgensen2Michael Bording-Jorgensen3Richard Chan4Richard Chan5Eytan Wine6Eytan Wine7Eytan Wine8Department of Pediatrics, University of Alberta, Edmonton, AB, CanadaCentre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR), University of Alberta, Edmonton, AB, CanadaCentre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR), University of Alberta, Edmonton, AB, CanadaDepartment of Physiology, University of Alberta, Edmonton, AB, CanadaCentre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR), University of Alberta, Edmonton, AB, CanadaDepartment of Physiology, University of Alberta, Edmonton, AB, CanadaDepartment of Pediatrics, University of Alberta, Edmonton, AB, CanadaCentre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR), University of Alberta, Edmonton, AB, CanadaDepartment of Physiology, University of Alberta, Edmonton, AB, CanadaAltered microbiota has been associated with a number of diseases, including inflammatory bowel diseases, diabetes, and cancer. This dysregulation is thought to relate the host inflammatory response to enteric pathogens. Macrophages play a key role in host response to microbes and are involved in bacterial killing and clearance. This process is partially mediated through the potassium efflux-dependent, cytosolic, PYCARD-containing inflammasome protein complex. Surprisingly, we discovered an alternative mechanism for bacterial killing, independent of the NLRP3 inflammasome/PYCARD. Using the NLRP3 inflammasome-deficient Raw 264.7 and PYCARD-deficient J77 macrophages, which both lack PYCARD, we found that the potassium efflux activator nigericin enhances bacterial killing. Macrophage response to nigericin was examined by RT gene profiling and subsequent qPCR, which demonstrated altered expression of a series of genes involved in the IL-18 bacterial killing pathway. Based on our results we propose a model of bacterial killing, unrelated to NLRP3 inflammasome activation in macrophage cells. Improving understanding of the molecular pathways driving bacterial clearance within macrophage cells will aid in the development of novel immune-targeted therapeutics in a number of diseases.https://www.frontiersin.org/article/10.3389/fimmu.2019.02296/fullNLRP3inflammasomeinflammatory bowel diseasesCitrobacter rodentiumnigericin |
| spellingShingle | Heather Armstrong Heather Armstrong Michael Bording-Jorgensen Michael Bording-Jorgensen Richard Chan Richard Chan Eytan Wine Eytan Wine Eytan Wine Nigericin Promotes NLRP3-Independent Bacterial Killing in Macrophages Frontiers in Immunology NLRP3 inflammasome inflammatory bowel diseases Citrobacter rodentium nigericin |
| title | Nigericin Promotes NLRP3-Independent Bacterial Killing in Macrophages |
| title_full | Nigericin Promotes NLRP3-Independent Bacterial Killing in Macrophages |
| title_fullStr | Nigericin Promotes NLRP3-Independent Bacterial Killing in Macrophages |
| title_full_unstemmed | Nigericin Promotes NLRP3-Independent Bacterial Killing in Macrophages |
| title_short | Nigericin Promotes NLRP3-Independent Bacterial Killing in Macrophages |
| title_sort | nigericin promotes nlrp3 independent bacterial killing in macrophages |
| topic | NLRP3 inflammasome inflammatory bowel diseases Citrobacter rodentium nigericin |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02296/full |
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