The role of caspase-1, caspase-4 and NLRP3 in regulating the host cell response evoked by uropathogenic Escherichia coli
Abstract The inflammasome-associated proteins caspase-1, caspase-4 and NLRP3 have been emphasised to be essential in the host cell response during urinary tract infection (UTI) by regulating IL-1β release. Our aim was to investigate how the inflammasome-associated proteins regulate the cell response...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-06052-7 |
| _version_ | 1818330307030417408 |
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| author | Anna Lindblad Charlotte Johansson Katarina Persson Isak Demirel |
| author_facet | Anna Lindblad Charlotte Johansson Katarina Persson Isak Demirel |
| author_sort | Anna Lindblad |
| collection | DOAJ |
| description | Abstract The inflammasome-associated proteins caspase-1, caspase-4 and NLRP3 have been emphasised to be essential in the host cell response during urinary tract infection (UTI) by regulating IL-1β release. Our aim was to investigate how the inflammasome-associated proteins regulate the cell response of bladder epithelial cells during infection with uropathogenic Escherichia coli (UPEC). Human bladder epithelial cells (5637) and CRISPR/Cas9 generated caspase-1, caspase-4 and NLRP3 knockdown cells were stimulated with the UPEC strain CFT073. Using Olink proteomics and real time RT-PCR, we showed that caspase-1, caspase-4 and NLRP3 are vital for the expression of many inflammatory genes and proteins from bladder epithelial cells. When investigating the effect of inflammasome-associated proteins on neutrophils, we found that conditioned medium from UPEC-infected caspase-4 knockdown cells significantly increased phagocytosis of CFT073 and significantly decreased ROS production from neutrophils. In contrast, conditioned medium from UPEC-infected NLRP3 knockdown cells significantly decreased the phagocytosis of CFT073 and significantly increased the ROS production from neutrophils. In conclusion, we showed that the inflammasome-associated proteins contribute to the host cell response during UPEC infection. |
| first_indexed | 2024-12-13T13:01:52Z |
| format | Article |
| id | doaj.art-5ea49cb7890d4a32af1474777bb382e7 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T13:01:52Z |
| publishDate | 2022-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5ea49cb7890d4a32af1474777bb382e72022-12-21T23:44:57ZengNature PortfolioScientific Reports2045-23222022-02-0112111110.1038/s41598-022-06052-7The role of caspase-1, caspase-4 and NLRP3 in regulating the host cell response evoked by uropathogenic Escherichia coliAnna Lindblad0Charlotte Johansson1Katarina Persson2Isak Demirel3School of Medical Sciences, Inflammatory Response and Infection Susceptibility Centre (iRiSC), Örebro UniversitySchool of Medical Sciences, Inflammatory Response and Infection Susceptibility Centre (iRiSC), Örebro UniversitySchool of Medical Sciences, Inflammatory Response and Infection Susceptibility Centre (iRiSC), Örebro UniversitySchool of Medical Sciences, Inflammatory Response and Infection Susceptibility Centre (iRiSC), Örebro UniversityAbstract The inflammasome-associated proteins caspase-1, caspase-4 and NLRP3 have been emphasised to be essential in the host cell response during urinary tract infection (UTI) by regulating IL-1β release. Our aim was to investigate how the inflammasome-associated proteins regulate the cell response of bladder epithelial cells during infection with uropathogenic Escherichia coli (UPEC). Human bladder epithelial cells (5637) and CRISPR/Cas9 generated caspase-1, caspase-4 and NLRP3 knockdown cells were stimulated with the UPEC strain CFT073. Using Olink proteomics and real time RT-PCR, we showed that caspase-1, caspase-4 and NLRP3 are vital for the expression of many inflammatory genes and proteins from bladder epithelial cells. When investigating the effect of inflammasome-associated proteins on neutrophils, we found that conditioned medium from UPEC-infected caspase-4 knockdown cells significantly increased phagocytosis of CFT073 and significantly decreased ROS production from neutrophils. In contrast, conditioned medium from UPEC-infected NLRP3 knockdown cells significantly decreased the phagocytosis of CFT073 and significantly increased the ROS production from neutrophils. In conclusion, we showed that the inflammasome-associated proteins contribute to the host cell response during UPEC infection.https://doi.org/10.1038/s41598-022-06052-7 |
| spellingShingle | Anna Lindblad Charlotte Johansson Katarina Persson Isak Demirel The role of caspase-1, caspase-4 and NLRP3 in regulating the host cell response evoked by uropathogenic Escherichia coli Scientific Reports |
| title | The role of caspase-1, caspase-4 and NLRP3 in regulating the host cell response evoked by uropathogenic Escherichia coli |
| title_full | The role of caspase-1, caspase-4 and NLRP3 in regulating the host cell response evoked by uropathogenic Escherichia coli |
| title_fullStr | The role of caspase-1, caspase-4 and NLRP3 in regulating the host cell response evoked by uropathogenic Escherichia coli |
| title_full_unstemmed | The role of caspase-1, caspase-4 and NLRP3 in regulating the host cell response evoked by uropathogenic Escherichia coli |
| title_short | The role of caspase-1, caspase-4 and NLRP3 in regulating the host cell response evoked by uropathogenic Escherichia coli |
| title_sort | role of caspase 1 caspase 4 and nlrp3 in regulating the host cell response evoked by uropathogenic escherichia coli |
| url | https://doi.org/10.1038/s41598-022-06052-7 |
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