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Wang, Xiao; Wang, Shuyan; Xu, Xiaoyan; Jiang, Yuzhu; Ren, Liqin; Zhang, Haixia; Li, Zhidan; Liu, Xianbing; Hu, Xuemei; Ren, Yushan
Parasites & vectors, 07/2024, Letnik: 17, Številka: 1Journal Article
Toxoplasma gondii infection causes adverse pregnancy outcomes by affecting the expression of immunotolerant molecules in decidual immune cells. Galectin-9 (Gal-9) is widely expressed in decidual macrophages (dMphi) and is crucial for maintaining normal pregnancy by interacting with the immunomodulatory protein T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3). However, the effects of T. gondii infection on Gal-9 expression in dMphi, and the impact of altered Gal-9 expression levels on the maternal-fetal tolerance function of decidual natural killer (dNK) cells, are still unknown. Pregnancy outcomes of T. gondii-infected C57BL/6 and Lgals9.sup.-/- pregnant mice models were recorded. Expression of Gal-9, c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), and Forkhead box protein O1 (FOXO1) was detected by western blotting, flow cytometry or immunofluorescence. The binding of FOXO1 to the promoter of Lgals9 was determined by chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR). The expression of extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK), cAMP-response element binding protein (CREB), phosphorylated CREB (p-CREB), T-box expressed in T cells (T-bet), interleukin 10 (IL-10), and interferon gamma (IFN-gamma) in dNK cells was assayed by western blotting. Toxoplasma gondii infection increased the expression of p-JNK and FOXO1 in dMphi, resulting in a reduction in Gal-9 due to the elevated binding of FOXO1 with Lgals9 promoter. Downregulation of Gal-9 enhanced the phosphorylation of ERK, inhibited the expression of p-CREB and IL-10, and promoted the expression of T-bet and IFN-gamma in dNK cells. In the mice model, knockout of Lgals9 aggravated adverse pregnancy outcomes caused by T. gondii infection during pregnancy. Toxoplasma gondii infection suppressed Gal-9 expression in dMphi by activating the JNK/FOXO1 signaling pathway, and reduction of Gal-9 contributed to dysfunction of dNK via Gal-9/Tim-3 interaction. This study provides new insights for the molecular mechanisms of the adverse pregnancy outcomes caused by T. gondii.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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