{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ma Z"],"funding":["National Natural Sciences Foundation of China"],"pagination":["454"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9724370"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["<h4>Background</h4>Toxoplasma gondii is known as the most successful parasite, which can regulate the host immune response through a variety of ways to achieve immune escape. We previously reported that a novel gene wx2 of T. gondii may be a virulence-related molecule. The objective of this study was to explore the mechanism of wx2 regulating host immune response.<h4>Methods</h4>The wx2 knockout strain (RH<sup>wx2-/-</sup> strain) and complementary strain (RH<sup>wx2+/+</sup> strain) were constructed by the CRISPR/Cas9 technique, and the virulence of the wx2 gene was detected and changes in pyroptosis-related molecules were observed.<h4>Results</h4>Compared with the wild RH and RH<sup>wx2+/+</sup> strain groups, the survival time for mice infected with the RH<sup>wx2-/-</sup> strain was prolonged to a certain extent. The mRNA levels of pyroptosis-related molecules of caspase-1, NLRP3, and GSDMD and et al. in mouse lymphocytes in vivo and RAW267.4 cells in vitro infected with RH<sup>wx2-/-</sup> strain increased to different degrees, compared with infected with wild RH strain and RH<sup>wx2+/+</sup> strain. As with the mRNA level, the protein level of caspase-1, caspase-1 p20, IL-1β, NLRP3, GSDMD-FL, GSDMD-N, and phosphorylation level of NF-κB (p65) were also significantly increased. These data suggest that wx2 may regulate the host immune response through the pyroptosis pathway. In infected RAW264.7 cells at 48 h post-infection, the levels of Th1-type cytokines of IFN-γ, Th2-type cytokines such as IL-13, Th17-type cytokine of IL-17 in cells infected with RH<sup>wx2-/-</sup> were significantly higher than those of RH and RH<sup>wx2+/+</sup> strains, suggesting that the wx2 may inhibit the host's immune response.<h4>Conclusion</h4>wx2 is a virulence related gene of T. gondii, and may be involved in host immune regulation by inhibiting the pyroptosis pathway."],"journal":["Parasites & vectors"],"pubmed_title":["Virulence-related gene wx2 of Toxoplasma gondii regulated host immune response via classic pyroptosis pathway."],"pmcid":["PMC9724370"],"funding_grant_id":["82072306"],"pubmed_authors":["Li X","Yan K","Li Z","Huang Y","Jiang R","Zhang N","Ma Z","Lu B","Dibo N","Wu X"],"additional_accession":[]},"is_claimable":false,"name":"Virulence-related gene wx2 of Toxoplasma gondii regulated host immune response via classic pyroptosis pathway.","description":"<h4>Background</h4>Toxoplasma gondii is known as the most successful parasite, which can regulate the host immune response through a variety of ways to achieve immune escape. We previously reported that a novel gene wx2 of T. gondii may be a virulence-related molecule. The objective of this study was to explore the mechanism of wx2 regulating host immune response.<h4>Methods</h4>The wx2 knockout strain (RH<sup>wx2-/-</sup> strain) and complementary strain (RH<sup>wx2+/+</sup> strain) were constructed by the CRISPR/Cas9 technique, and the virulence of the wx2 gene was detected and changes in pyroptosis-related molecules were observed.<h4>Results</h4>Compared with the wild RH and RH<sup>wx2+/+</sup> strain groups, the survival time for mice infected with the RH<sup>wx2-/-</sup> strain was prolonged to a certain extent. The mRNA levels of pyroptosis-related molecules of caspase-1, NLRP3, and GSDMD and et al. in mouse lymphocytes in vivo and RAW267.4 cells in vitro infected with RH<sup>wx2-/-</sup> strain increased to different degrees, compared with infected with wild RH strain and RH<sup>wx2+/+</sup> strain. As with the mRNA level, the protein level of caspase-1, caspase-1 p20, IL-1β, NLRP3, GSDMD-FL, GSDMD-N, and phosphorylation level of NF-κB (p65) were also significantly increased. These data suggest that wx2 may regulate the host immune response through the pyroptosis pathway. In infected RAW264.7 cells at 48 h post-infection, the levels of Th1-type cytokines of IFN-γ, Th2-type cytokines such as IL-13, Th17-type cytokine of IL-17 in cells infected with RH<sup>wx2-/-</sup> were significantly higher than those of RH and RH<sup>wx2+/+</sup> strains, suggesting that the wx2 may inhibit the host's immune response.<h4>Conclusion</h4>wx2 is a virulence related gene of T. gondii, and may be involved in host immune regulation by inhibiting the pyroptosis pathway.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2025-04-19T13:22:09.833Z","creation":"2025-04-19T13:22:09.833Z"},"accession":"S-EPMC9724370","cross_references":{"pubmed":["36471417"],"doi":["10.1186/s13071-022-05502-5"]}}