Giardia VSPAS7 protein attenuates Giardia intestinalis-induced host macrophage pyroptosis
Abstract Background The unicellular protozoan parasite Giardia intestinalis, which primarily infects humans and animals such as cattle and sheep, is having a major negative impact on public health. Giardia is able to evade the recognition and elimination of the host immune system because of the trop...
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Parasites & Vectors |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13071-023-05949-0 |
| _version_ | 1827635399303888896 |
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| author | Min Sun Zhiteng Zhao Ying Li Lili Cao Jianhua Li Xichen Zhang Xin Li Nan Zhang Shuqin Cheng Xiaocen Wang Pengtao Gong |
| author_facet | Min Sun Zhiteng Zhao Ying Li Lili Cao Jianhua Li Xichen Zhang Xin Li Nan Zhang Shuqin Cheng Xiaocen Wang Pengtao Gong |
| author_sort | Min Sun |
| collection | DOAJ |
| description | Abstract Background The unicellular protozoan parasite Giardia intestinalis, which primarily infects humans and animals such as cattle and sheep, is having a major negative impact on public health. Giardia is able to evade the recognition and elimination of the host immune system because of the trophozoite surface and extracellular vesicles (EVs) covered by variant-specific surface proteins (VSPs). As key proteins for immune evasion, whether VSPs can regulate Giardia-induced pyroptosis and promote Giardia evasion of host immune responses has not been reported. Methods To examine the role of Giardia VSPAS7 on Giardia-induced activation of the signaling pathway, secretion of pro-inflammatory cytokines, pyroptosis and the mechanism involved, we constructed the pcDNA3.1-vspas7 expression plasmid and transfected this plasmid into mouse macrophages. Key proteins for pyroptosis, IL-1β secretion and LDH release were detected in pcDNA3.1-vspas7-transfected wild-type (WT) cells and NLRP3-deficient cells by western blot, ELISA and LDH assays, respectively. The interactions of Giardia VSPAS7 and mouse NLRP3 were examined using immunofluorescence assays (IFA), co-immunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC) assays. Results VSPAS7 could decrease the levels of phosphorylated-p65 (P-p65), P-IκBα and P-ERK caused by Giardia and reduce the production levels of Giardia-induced pro-inflammatory cytokine IL-6, IL-12 p40 and TNF-α. The results showed that VSPAS7 inhibited Giardia-mediated activation of NF-κB, ERK/MAPK signaling and secretion of pro-inflammatory cytokines. Furthermore, VSPAS7 suppressed Giardia-induced macrophage pyroptosis by reducing GSDMD cleavage, caspase-1 activation, IL-1β secretion and LDH release. We further found that VSPAS7 could interact with mouse NLRP3 directly, and in NLRP3-deficient cells the suppression of Giardia-induced macrophage pyroptosis by VSPAS7 was significantly attenuated. Conclusions Overall, VSPAS7 could inhibit Giardia-induced activation of signaling pathways and pyroptosis in host macrophages, allowing Giardia evasion of host immune responses. Studies on Giardia VSP-mediated immune evasion provide an important theoretical basis for in-depth studies on Giardia pathogenicity. Graphical abstract |
| first_indexed | 2024-03-09T15:27:09Z |
| format | Article |
| id | doaj.art-54d058e611b649939046b8cb14c999eb |
| institution | Directory Open Access Journal |
| issn | 1756-3305 |
| language | English |
| last_indexed | 2024-03-09T15:27:09Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Parasites & Vectors |
| spelling | doaj.art-54d058e611b649939046b8cb14c999eb2023-11-26T12:28:58ZengBMCParasites & Vectors1756-33052023-10-0116111510.1186/s13071-023-05949-0Giardia VSPAS7 protein attenuates Giardia intestinalis-induced host macrophage pyroptosisMin Sun0Zhiteng Zhao1Ying Li2Lili Cao3Jianhua Li4Xichen Zhang5Xin Li6Nan Zhang7Shuqin Cheng8Xiaocen Wang9Pengtao Gong10State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityJilin Academy of Animal Husbandry and Veterinary MedicineState Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityAbstract Background The unicellular protozoan parasite Giardia intestinalis, which primarily infects humans and animals such as cattle and sheep, is having a major negative impact on public health. Giardia is able to evade the recognition and elimination of the host immune system because of the trophozoite surface and extracellular vesicles (EVs) covered by variant-specific surface proteins (VSPs). As key proteins for immune evasion, whether VSPs can regulate Giardia-induced pyroptosis and promote Giardia evasion of host immune responses has not been reported. Methods To examine the role of Giardia VSPAS7 on Giardia-induced activation of the signaling pathway, secretion of pro-inflammatory cytokines, pyroptosis and the mechanism involved, we constructed the pcDNA3.1-vspas7 expression plasmid and transfected this plasmid into mouse macrophages. Key proteins for pyroptosis, IL-1β secretion and LDH release were detected in pcDNA3.1-vspas7-transfected wild-type (WT) cells and NLRP3-deficient cells by western blot, ELISA and LDH assays, respectively. The interactions of Giardia VSPAS7 and mouse NLRP3 were examined using immunofluorescence assays (IFA), co-immunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC) assays. Results VSPAS7 could decrease the levels of phosphorylated-p65 (P-p65), P-IκBα and P-ERK caused by Giardia and reduce the production levels of Giardia-induced pro-inflammatory cytokine IL-6, IL-12 p40 and TNF-α. The results showed that VSPAS7 inhibited Giardia-mediated activation of NF-κB, ERK/MAPK signaling and secretion of pro-inflammatory cytokines. Furthermore, VSPAS7 suppressed Giardia-induced macrophage pyroptosis by reducing GSDMD cleavage, caspase-1 activation, IL-1β secretion and LDH release. We further found that VSPAS7 could interact with mouse NLRP3 directly, and in NLRP3-deficient cells the suppression of Giardia-induced macrophage pyroptosis by VSPAS7 was significantly attenuated. Conclusions Overall, VSPAS7 could inhibit Giardia-induced activation of signaling pathways and pyroptosis in host macrophages, allowing Giardia evasion of host immune responses. Studies on Giardia VSP-mediated immune evasion provide an important theoretical basis for in-depth studies on Giardia pathogenicity. Graphical abstracthttps://doi.org/10.1186/s13071-023-05949-0Giardia intestinalisVSPAS7NLRP3Pyroptosis |
| spellingShingle | Min Sun Zhiteng Zhao Ying Li Lili Cao Jianhua Li Xichen Zhang Xin Li Nan Zhang Shuqin Cheng Xiaocen Wang Pengtao Gong Giardia VSPAS7 protein attenuates Giardia intestinalis-induced host macrophage pyroptosis Parasites & Vectors Giardia intestinalis VSPAS7 NLRP3 Pyroptosis |
| title | Giardia VSPAS7 protein attenuates Giardia intestinalis-induced host macrophage pyroptosis |
| title_full | Giardia VSPAS7 protein attenuates Giardia intestinalis-induced host macrophage pyroptosis |
| title_fullStr | Giardia VSPAS7 protein attenuates Giardia intestinalis-induced host macrophage pyroptosis |
| title_full_unstemmed | Giardia VSPAS7 protein attenuates Giardia intestinalis-induced host macrophage pyroptosis |
| title_short | Giardia VSPAS7 protein attenuates Giardia intestinalis-induced host macrophage pyroptosis |
| title_sort | giardia vspas7 protein attenuates giardia intestinalis induced host macrophage pyroptosis |
| topic | Giardia intestinalis VSPAS7 NLRP3 Pyroptosis |
| url | https://doi.org/10.1186/s13071-023-05949-0 |
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