Expression profiles of NOD-like receptors and regulation of NLRP3 inflammasome activation in Toxoplasma gondii-infected human small intestinal epithelial cells
Abstract Background Toxoplasma gondii is a parasite that primarily infects through the oral route. Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) play crucial roles in the immune responses generated during parasitic infection and also drive the inflammatory response against in...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-03-01
|
| Series: | Parasites & Vectors |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13071-021-04666-w |
| _version_ | 1818870752197214208 |
|---|---|
| author | Jia-Qi Chu Fei Fei Gao Weiyun Wu Chunchao Li Zhaobin Pan Jinhui Sun Hao Wang Cong Huang Sang Hyuk Lee Juan-Hua Quan Young-Ha Lee |
| author_facet | Jia-Qi Chu Fei Fei Gao Weiyun Wu Chunchao Li Zhaobin Pan Jinhui Sun Hao Wang Cong Huang Sang Hyuk Lee Juan-Hua Quan Young-Ha Lee |
| author_sort | Jia-Qi Chu |
| collection | DOAJ |
| description | Abstract Background Toxoplasma gondii is a parasite that primarily infects through the oral route. Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) play crucial roles in the immune responses generated during parasitic infection and also drive the inflammatory response against invading parasites. However, little is known about the regulation of NLRs and inflammasome activation in T. gondii-infected human small intestinal epithelial (FHs 74 Int) cells. Methods FHs 74 Int cells infected with T. gondii were subsequently evaluated for morphological changes, cytotoxicity, expression profiles of NLRs, inflammasome components, caspase-cleaved interleukins (ILs), and the mechanisms of NLRP3 and NLRP6 inflammasome activation. Immunocytochemistry, lactate dehydrogenase assay, reverse transcription polymerase chain reaction (RT-PCR), real-time quantitative RT-PCR, and western blotting techniques were utilized for analysis. Results Under normal and T. gondii-infected conditions, members of the NLRs, inflammasome components and caspase-cleaved ILs were expressed in the FHs Int 74 cells, except for NLRC3, NLRP5, and NLRP9. Among the NLRs, mRNA expression of NOD2, NLRP3, NLRP6, and NAIP1 was significantly increased in T. gondii-infected cells, whereas that of NLRP2, NLRP7, and CIITA mRNAs decreased significantly in a time-dependent manner. In addition, T. gondii infection induced NLRP3, NLRP6 and NLRC4 inflammasome activation and production of IL-1β, IL-18, and IL-33 in FHs 74 Int cells. T. gondii-induced NLRP3 inflammasome activation was strongly associated with the phosphorylation of p38 MAPK; however, JNK1/2 had a weak effect. NLRP6 inflammasome activation was not related to the MAPK pathway in FHs 74 Int cells. Conclusions This study highlighted the expression profiles of NLRs and unraveled the underlying mechanisms of NLRP3 inflammasome activation in T. gondii-infected FHs 74 Int cells. These findings may contribute to understanding of the mucosal and innate immune responses induced by the NLRs and inflammasomes during T. gondii infection in FHs 74 Int cells. |
| first_indexed | 2024-12-19T12:12:01Z |
| format | Article |
| id | doaj.art-b3f76f4326ef413794cb2195e7935578 |
| institution | Directory Open Access Journal |
| issn | 1756-3305 |
| language | English |
| last_indexed | 2024-12-19T12:12:01Z |
| publishDate | 2021-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Parasites & Vectors |
| spelling | doaj.art-b3f76f4326ef413794cb2195e79355782022-12-21T20:22:10ZengBMCParasites & Vectors1756-33052021-03-0114111310.1186/s13071-021-04666-wExpression profiles of NOD-like receptors and regulation of NLRP3 inflammasome activation in Toxoplasma gondii-infected human small intestinal epithelial cellsJia-Qi Chu0Fei Fei Gao1Weiyun Wu2Chunchao Li3Zhaobin Pan4Jinhui Sun5Hao Wang6Cong Huang7Sang Hyuk Lee8Juan-Hua Quan9Young-Ha Lee10Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical UniversityBrain Korea 21 FOUR Project for Medical Science, Chungnam National UniversityDepartment of Gastroenterology, Affiliated Hospital of Guangdong Medical UniversityDepartment of Gastroenterology, Affiliated Hospital of Guangdong Medical UniversityDepartment of Gastroenterology, Affiliated Hospital of Guangdong Medical UniversityDepartment of Gastroenterology, Affiliated Hospital of Guangdong Medical UniversityDepartment of Gastroenterology, Affiliated Hospital of Guangdong Medical UniversityDepartment of Dermatology, Skin Research Institute of Peking University Shenzhen Hospital, Peking University Shenzhen HospitalDepartment of Internal Medicine, Sun General HospitalDepartment of Gastroenterology, Affiliated Hospital of Guangdong Medical UniversityBrain Korea 21 FOUR Project for Medical Science, Chungnam National UniversityAbstract Background Toxoplasma gondii is a parasite that primarily infects through the oral route. Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) play crucial roles in the immune responses generated during parasitic infection and also drive the inflammatory response against invading parasites. However, little is known about the regulation of NLRs and inflammasome activation in T. gondii-infected human small intestinal epithelial (FHs 74 Int) cells. Methods FHs 74 Int cells infected with T. gondii were subsequently evaluated for morphological changes, cytotoxicity, expression profiles of NLRs, inflammasome components, caspase-cleaved interleukins (ILs), and the mechanisms of NLRP3 and NLRP6 inflammasome activation. Immunocytochemistry, lactate dehydrogenase assay, reverse transcription polymerase chain reaction (RT-PCR), real-time quantitative RT-PCR, and western blotting techniques were utilized for analysis. Results Under normal and T. gondii-infected conditions, members of the NLRs, inflammasome components and caspase-cleaved ILs were expressed in the FHs Int 74 cells, except for NLRC3, NLRP5, and NLRP9. Among the NLRs, mRNA expression of NOD2, NLRP3, NLRP6, and NAIP1 was significantly increased in T. gondii-infected cells, whereas that of NLRP2, NLRP7, and CIITA mRNAs decreased significantly in a time-dependent manner. In addition, T. gondii infection induced NLRP3, NLRP6 and NLRC4 inflammasome activation and production of IL-1β, IL-18, and IL-33 in FHs 74 Int cells. T. gondii-induced NLRP3 inflammasome activation was strongly associated with the phosphorylation of p38 MAPK; however, JNK1/2 had a weak effect. NLRP6 inflammasome activation was not related to the MAPK pathway in FHs 74 Int cells. Conclusions This study highlighted the expression profiles of NLRs and unraveled the underlying mechanisms of NLRP3 inflammasome activation in T. gondii-infected FHs 74 Int cells. These findings may contribute to understanding of the mucosal and innate immune responses induced by the NLRs and inflammasomes during T. gondii infection in FHs 74 Int cells.https://doi.org/10.1186/s13071-021-04666-wToxoplasma gondiiHuman small intestinal epithelial cellsNOD-like receptorsInflammasomeCaspase-cleaved interleukins |
| spellingShingle | Jia-Qi Chu Fei Fei Gao Weiyun Wu Chunchao Li Zhaobin Pan Jinhui Sun Hao Wang Cong Huang Sang Hyuk Lee Juan-Hua Quan Young-Ha Lee Expression profiles of NOD-like receptors and regulation of NLRP3 inflammasome activation in Toxoplasma gondii-infected human small intestinal epithelial cells Parasites & Vectors Toxoplasma gondii Human small intestinal epithelial cells NOD-like receptors Inflammasome Caspase-cleaved interleukins |
| title | Expression profiles of NOD-like receptors and regulation of NLRP3 inflammasome activation in Toxoplasma gondii-infected human small intestinal epithelial cells |
| title_full | Expression profiles of NOD-like receptors and regulation of NLRP3 inflammasome activation in Toxoplasma gondii-infected human small intestinal epithelial cells |
| title_fullStr | Expression profiles of NOD-like receptors and regulation of NLRP3 inflammasome activation in Toxoplasma gondii-infected human small intestinal epithelial cells |
| title_full_unstemmed | Expression profiles of NOD-like receptors and regulation of NLRP3 inflammasome activation in Toxoplasma gondii-infected human small intestinal epithelial cells |
| title_short | Expression profiles of NOD-like receptors and regulation of NLRP3 inflammasome activation in Toxoplasma gondii-infected human small intestinal epithelial cells |
| title_sort | expression profiles of nod like receptors and regulation of nlrp3 inflammasome activation in toxoplasma gondii infected human small intestinal epithelial cells |
| topic | Toxoplasma gondii Human small intestinal epithelial cells NOD-like receptors Inflammasome Caspase-cleaved interleukins |
| url | https://doi.org/10.1186/s13071-021-04666-w |
| work_keys_str_mv | AT jiaqichu expressionprofilesofnodlikereceptorsandregulationofnlrp3inflammasomeactivationintoxoplasmagondiiinfectedhumansmallintestinalepithelialcells AT feifeigao expressionprofilesofnodlikereceptorsandregulationofnlrp3inflammasomeactivationintoxoplasmagondiiinfectedhumansmallintestinalepithelialcells AT weiyunwu expressionprofilesofnodlikereceptorsandregulationofnlrp3inflammasomeactivationintoxoplasmagondiiinfectedhumansmallintestinalepithelialcells AT chunchaoli expressionprofilesofnodlikereceptorsandregulationofnlrp3inflammasomeactivationintoxoplasmagondiiinfectedhumansmallintestinalepithelialcells AT zhaobinpan expressionprofilesofnodlikereceptorsandregulationofnlrp3inflammasomeactivationintoxoplasmagondiiinfectedhumansmallintestinalepithelialcells AT jinhuisun expressionprofilesofnodlikereceptorsandregulationofnlrp3inflammasomeactivationintoxoplasmagondiiinfectedhumansmallintestinalepithelialcells AT haowang expressionprofilesofnodlikereceptorsandregulationofnlrp3inflammasomeactivationintoxoplasmagondiiinfectedhumansmallintestinalepithelialcells AT conghuang expressionprofilesofnodlikereceptorsandregulationofnlrp3inflammasomeactivationintoxoplasmagondiiinfectedhumansmallintestinalepithelialcells AT sanghyuklee expressionprofilesofnodlikereceptorsandregulationofnlrp3inflammasomeactivationintoxoplasmagondiiinfectedhumansmallintestinalepithelialcells AT juanhuaquan expressionprofilesofnodlikereceptorsandregulationofnlrp3inflammasomeactivationintoxoplasmagondiiinfectedhumansmallintestinalepithelialcells AT younghalee expressionprofilesofnodlikereceptorsandregulationofnlrp3inflammasomeactivationintoxoplasmagondiiinfectedhumansmallintestinalepithelialcells |