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Trichomonas vaginalis Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages
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| Zeitschriftentitel: | Journal of Innate Immunity |
|---|---|
| Personen und Körperschaften: | , , , , , , |
| In: | Journal of Innate Immunity, 11, 2019, 1, S. 86-98 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
S. Karger AG
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| Schlagwörter: |
| author_facet |
Riestra, Angelica Montenegro Valderrama, J. Andrés Patras, Kathryn A. Booth, Sharon D. Quek, Xing Yen Tsai, Chih-Ming Nizet, Victor Riestra, Angelica Montenegro Valderrama, J. Andrés Patras, Kathryn A. Booth, Sharon D. Quek, Xing Yen Tsai, Chih-Ming Nizet, Victor |
|---|---|
| author |
Riestra, Angelica Montenegro Valderrama, J. Andrés Patras, Kathryn A. Booth, Sharon D. Quek, Xing Yen Tsai, Chih-Ming Nizet, Victor |
| spellingShingle |
Riestra, Angelica Montenegro Valderrama, J. Andrés Patras, Kathryn A. Booth, Sharon D. Quek, Xing Yen Tsai, Chih-Ming Nizet, Victor Journal of Innate Immunity Trichomonas vaginalis Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages Immunology and Allergy |
| author_sort |
riestra, angelica montenegro |
| spelling |
Riestra, Angelica Montenegro Valderrama, J. Andrés Patras, Kathryn A. Booth, Sharon D. Quek, Xing Yen Tsai, Chih-Ming Nizet, Victor 1662-811X 1662-8128 S. Karger AG Immunology and Allergy http://dx.doi.org/10.1159/000493585 <jats:p><i>Trichomonas vaginalis</i> is a sexually transmitted, eukaryotic parasite that causes trichomoniasis, the most common nonviral, sexually transmitted disease in the USA and worldwide. Little is known about the molecular mechanisms involved in the host immune response to this widespread parasite. Here we report that <i>T. vaginalis</i> induces NLRP3 inflammasome activation in human macrophages, leading to caspase-1 activation and the processing of pro-IL-1β to the mature and bioactive form of the cytokine. Using inhibitor-based approaches, we show that NLRP3 activation by <i>T. vaginalis</i> involves host cell detection of extracellular ATP via P2X<sub>7</sub> receptors and potassium efflux. In addition, our data reveal that <i>T. vaginalis</i> inflammasome activation induces macrophage inflammatory cell death by pyroptosis, known to occur via caspase-1 cleavage of the gasdermin D protein, which assembles to form pores in the host cell membrane. We found that <i>T. vaginalis</i>-induced cytolysis of macrophages is attenuated in gasdermin D knockout cells. Lastly, in a murine challenge model, we detected IL-1β production in vaginal fluids in response to <i>T. vaginalis</i> infection in vivo. Together, our findings mechanistically dissect how <i>T. vaginalis</i> contributes to the production of the proinflammatory IL-1β cytokine and uncover pyroptosis as a mechanism by which the parasite can trigger host macrophage cell death.</jats:p> <b><i>Trichomonas vaginalis</i></b> Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages Journal of Innate Immunity |
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S. Karger AG, 2019 |
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1662-811X 1662-8128 |
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Journal of Innate Immunity |
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| title |
Trichomonas vaginalis Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages |
| title_unstemmed |
Trichomonas vaginalis Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages |
| title_full |
Trichomonas vaginalis Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages |
| title_fullStr |
Trichomonas vaginalis Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages |
| title_full_unstemmed |
Trichomonas vaginalis Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages |
| title_short |
Trichomonas vaginalis Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages |
| title_sort |
<b><i>trichomonas vaginalis</i></b> induces nlrp3 inflammasome activation and pyroptotic cell death in human macrophages |
| topic |
Immunology and Allergy |
| url |
http://dx.doi.org/10.1159/000493585 |
| publishDate |
2019 |
| physical |
86-98 |
| description |
<jats:p><i>Trichomonas vaginalis</i> is a sexually transmitted, eukaryotic parasite that causes trichomoniasis, the most common nonviral, sexually transmitted disease in the USA and worldwide. Little is known about the molecular mechanisms involved in the host immune response to this widespread parasite. Here we report that <i>T. vaginalis</i> induces NLRP3 inflammasome activation in human macrophages, leading to caspase-1 activation and the processing of pro-IL-1β to the mature and bioactive form of the cytokine. Using inhibitor-based approaches, we show that NLRP3 activation by <i>T. vaginalis</i> involves host cell detection of extracellular ATP via P2X<sub>7</sub> receptors and potassium efflux. In addition, our data reveal that <i>T. vaginalis</i> inflammasome activation induces macrophage inflammatory cell death by pyroptosis, known to occur via caspase-1 cleavage of the gasdermin D protein, which assembles to form pores in the host cell membrane. We found that <i>T. vaginalis</i>-induced cytolysis of macrophages is attenuated in gasdermin D knockout cells. Lastly, in a murine challenge model, we detected IL-1β production in vaginal fluids in response to <i>T. vaginalis</i> infection in vivo. Together, our findings mechanistically dissect how <i>T. vaginalis</i> contributes to the production of the proinflammatory IL-1β cytokine and uncover pyroptosis as a mechanism by which the parasite can trigger host macrophage cell death.</jats:p> |
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| author | Riestra, Angelica Montenegro, Valderrama, J. Andrés, Patras, Kathryn A., Booth, Sharon D., Quek, Xing Yen, Tsai, Chih-Ming, Nizet, Victor |
| author_facet | Riestra, Angelica Montenegro, Valderrama, J. Andrés, Patras, Kathryn A., Booth, Sharon D., Quek, Xing Yen, Tsai, Chih-Ming, Nizet, Victor, Riestra, Angelica Montenegro, Valderrama, J. Andrés, Patras, Kathryn A., Booth, Sharon D., Quek, Xing Yen, Tsai, Chih-Ming, Nizet, Victor |
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| description | <jats:p><i>Trichomonas vaginalis</i> is a sexually transmitted, eukaryotic parasite that causes trichomoniasis, the most common nonviral, sexually transmitted disease in the USA and worldwide. Little is known about the molecular mechanisms involved in the host immune response to this widespread parasite. Here we report that <i>T. vaginalis</i> induces NLRP3 inflammasome activation in human macrophages, leading to caspase-1 activation and the processing of pro-IL-1β to the mature and bioactive form of the cytokine. Using inhibitor-based approaches, we show that NLRP3 activation by <i>T. vaginalis</i> involves host cell detection of extracellular ATP via P2X<sub>7</sub> receptors and potassium efflux. In addition, our data reveal that <i>T. vaginalis</i> inflammasome activation induces macrophage inflammatory cell death by pyroptosis, known to occur via caspase-1 cleavage of the gasdermin D protein, which assembles to form pores in the host cell membrane. We found that <i>T. vaginalis</i>-induced cytolysis of macrophages is attenuated in gasdermin D knockout cells. Lastly, in a murine challenge model, we detected IL-1β production in vaginal fluids in response to <i>T. vaginalis</i> infection in vivo. Together, our findings mechanistically dissect how <i>T. vaginalis</i> contributes to the production of the proinflammatory IL-1β cytokine and uncover pyroptosis as a mechanism by which the parasite can trigger host macrophage cell death.</jats:p> |
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| spelling | Riestra, Angelica Montenegro Valderrama, J. Andrés Patras, Kathryn A. Booth, Sharon D. Quek, Xing Yen Tsai, Chih-Ming Nizet, Victor 1662-811X 1662-8128 S. Karger AG Immunology and Allergy http://dx.doi.org/10.1159/000493585 <jats:p><i>Trichomonas vaginalis</i> is a sexually transmitted, eukaryotic parasite that causes trichomoniasis, the most common nonviral, sexually transmitted disease in the USA and worldwide. Little is known about the molecular mechanisms involved in the host immune response to this widespread parasite. Here we report that <i>T. vaginalis</i> induces NLRP3 inflammasome activation in human macrophages, leading to caspase-1 activation and the processing of pro-IL-1β to the mature and bioactive form of the cytokine. Using inhibitor-based approaches, we show that NLRP3 activation by <i>T. vaginalis</i> involves host cell detection of extracellular ATP via P2X<sub>7</sub> receptors and potassium efflux. In addition, our data reveal that <i>T. vaginalis</i> inflammasome activation induces macrophage inflammatory cell death by pyroptosis, known to occur via caspase-1 cleavage of the gasdermin D protein, which assembles to form pores in the host cell membrane. We found that <i>T. vaginalis</i>-induced cytolysis of macrophages is attenuated in gasdermin D knockout cells. Lastly, in a murine challenge model, we detected IL-1β production in vaginal fluids in response to <i>T. vaginalis</i> infection in vivo. Together, our findings mechanistically dissect how <i>T. vaginalis</i> contributes to the production of the proinflammatory IL-1β cytokine and uncover pyroptosis as a mechanism by which the parasite can trigger host macrophage cell death.</jats:p> <b><i>Trichomonas vaginalis</i></b> Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages Journal of Innate Immunity |
| spellingShingle | Riestra, Angelica Montenegro, Valderrama, J. Andrés, Patras, Kathryn A., Booth, Sharon D., Quek, Xing Yen, Tsai, Chih-Ming, Nizet, Victor, Journal of Innate Immunity, Trichomonas vaginalis Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages, Immunology and Allergy |
| title | Trichomonas vaginalis Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages |
| title_full | Trichomonas vaginalis Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages |
| title_fullStr | Trichomonas vaginalis Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages |
| title_full_unstemmed | Trichomonas vaginalis Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages |
| title_short | Trichomonas vaginalis Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages |
| title_sort | <b><i>trichomonas vaginalis</i></b> induces nlrp3 inflammasome activation and pyroptotic cell death in human macrophages |
| title_unstemmed | Trichomonas vaginalis Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages |
| topic | Immunology and Allergy |
| url | http://dx.doi.org/10.1159/000493585 |