Toxoplasma gondii Cathepsin C1 inhibits NF-κB signalling through the positive regulation of the HIF-1α/EPO axis

Liu, Yumei; Zou, Xiaoqian; Ou, Minglin; Ye, Xiaohong; Zhang, Baohuan; Wu, Tianyuan; Dong, Shihua; Chen, Xiaojing; Liu, Hongxuan; Zheng, Zhong; Zhao, Jierong; Wu, Jing; Liu, Dandan; Wen, Zihao; Wang, Yao; Zheng, Shimin; Zhu, Kui; Huang, Xueling; Du, Xiuben; Liang, Jiayu; Luo, Xiaolu; Xie, Yuefeng; Wu, Min; Lu, Congying; Xie, Xing; Liu, Kailiang; Ying, Yan; Qi, Guolong; Jing, Chunxia; Yang, Guang

doi:10.1016/j.actatropica.2019.04.018

Cited by 11 publications

(9 citation statements)

References 41 publications

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“…The release of IL-1 and IL-18 is typically considered to be downstream of inflammasome-mediated caspase activation and processing of pro-forms of these cytokines ( Man and Kanneganti, 2015 ). While there is evidence that pro-IL-1 and pro-IL-18 are produced during toxoplasmosis ( Hunter et al, 1993 ; Zediak and Hunter, 2003 ), several studies have concluded that T. gondii does not readily activate inflammasomes and there is evidence that Toxoplasma suppresses inflammasome activity ( Ewald et al, 2014 ; Lima et al, 2018 ; Liu et al, 2019 ). However, there is a report that the inflammasome sensors NLRP1 and NLRP3 are required for protective immunity to T. gondii ( Gorfu et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii

Clark

Christian

Gullicksrud

et al. 2021

eLife

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IL-33 is an alarmin required for resistance to the parasite Toxoplasma gondii, but its role in innate resistance to this organism is unclear. Infection with T. gondii promotes increased stromal cell expression of IL-33, and levels of parasite replication correlate with release of IL-33 in affected tissues. In response to infection, a subset of innate lymphoid cells (ILC) emerges composed of IL-33R+ NK cells and ILC1s. In Rag1−/−mice, where NK cells and ILC1 production of IFN-γ mediate innate resistance to T. gondii, the loss of the IL-33R resulted in reduced ILC responses and increased parasite replication. Furthermore, administration of IL-33 to Rag1−/− mice resulted in a marked decrease in parasite burden, increased production of IFN-γ, and the recruitment and expansion of inflammatory monocytes associated with parasite control. These protective effects of exogenous IL-33 were dependent on endogenous IL-12p40 and the ability of IL-33 to enhance ILC production of IFN-γ. These results highlight that IL-33 synergizes with IL-12 to promote ILC-mediated resistance to T. gondii.

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Section: Discussionmentioning

confidence: 99%

IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii

Clark

Christian

Gullicksrud

et al. 2021

eLife

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“…The results of the GO analysis of the glycosylated proteins after T. gondii infection in cats suggested that several special GO terms, such as biological regulation and response to stimulus, that play important roles in the NF-κB signaling pathway and the regulation of MIC protein were enriched in T. gondii and the cats [ 36 , 37 ]. The cell junction term plays an important role in maintaining the invasive force of T. gondii [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Glycosylation Analysis of Feline Small Intestine Following Toxoplasma gondii Infection

Zhai

Xie

Peng

et al. 2022

Animals

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Toxoplasma gondii (T. gondii) is responsible for severe human and livestock diseases, huge economic losses, and adversely affects the health of the public and the development of animal husbandry. Glycosylation is a common posttranslational modification of proteins in eukaryotes, and N-glycosylation is closely related to the biological functions of proteins. However, glycosylation alterations in the feline small intestine following T. gondii infection have not been reported. In this study, the experimental group was intragastrically challenged with 600 brain cysts of the Prugniuad (Pru) strain that were collected from infected mice. The cats’ intestinal epithelial tissues were harvested at 10 days post-infection and then sent for protein glycosylation analysis. High-performance liquid chromatography coupled to tandem mass spectrometry was used to analyze the glycosylation alterations in the small intestine of cats infected with T. gondii. The results of the present study showed that 56 glycosylated peptides were upregulated and 37 glycosylated peptides were downregulated in the feline small intestine infected by T. gondii. Additionally, we also identified eight N-glycosylated proteins of T. gondii including eight N-glycopeptides and eight N-glycosylation sites. The protein A0A086JND6_TOXGO (eEF2) and its corresponding peptide sequence were identified in T. gondii infection. Some special GO terms (i.e., cellular process and metabolic process, cell and cell part, and catalytic activity) were significantly enriched, and the Clusters of Orthologous Groups of proteins (COG) function prediction results showed that posttranslational modification, protein turnover, and chaperones (11%) had the highest enrichment for T. gondii. Interestingly, eEF2, a protein of T. gondii, is also involved in the significantly enriched T. gondii MAPK pathway. The host proteins ICAM-1 and PPT1 and the endoplasmic reticulum stress pathway may play an important role in the glycosylation of Toxoplasma-infected hosts. This is the first report showing that T. gondii oocysts can undergo N-glycosylation in the definitive host and that eEF2 is involved, which may provide a new target for T. gondii detection to prevent the spread of T. gondii oocysts in the future.

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“…The release of IL-1 and IL-18 is typically considered to be downstream of inflammasome mediated caspase activation and processing of pro-forms of these cytokines [89]. While there is evidence that pro-IL-1 and pro-IL-18 are produced during toxoplasmosis [31], [90]) several studies have concluded that T. gondii does not readily activate inflammasomes and there is evidence that Toxoplasma suppresses inflammasome activity [40], [91], [92]. However, there is a report that the inflammasome sensors NLRP1 and NLRP3 are required for protective immunity to T. gondii [41].…”

Section: Discussionmentioning

confidence: 99%

IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity toToxoplasma gondii

Clark

Christian

Gullicksrud

et al. 2021

Preprint

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IL-33 is an alarmin required for resistance to the parasite Toxoplasma gondii, but its role in innate resistance to this infection is unclear. T. gondii infection promotes increased stromal cell expression of IL-33 and levels of parasite replication correlate with IL-33 release. In response to infection, a subset of innate lymphoid cells (ILC) emerges composed of IL-33R+ NK cells and ILC1s. In Rag-/- mice, where NK cells and ILC1 provide an innate mechanism of resistance to T. gondii, the loss of IL-33R reduced ILC responses and increased parasite replication. Furthermore, administration of IL-33 to Rag-/- mice resulted in a marked decrease in parasite burden, increased production of IFN-γ and the recruitment and expansion of inflammatory monocytes associated with parasite control. These protective effects of exogenous IL-33 were dependent on endogenous IL-12p40 and the ability of IL-33 to enhance ILC production of IFN-γ. These results highlight that IL-33 synergizes with IL-12 to promote ILC-mediated resistance to T. gondii.

show abstract

Toxoplasma gondii Cathepsin C1 inhibits NF-κB signalling through the positive regulation of the HIF-1α/EPO axis

Cited by 11 publications

References 41 publications

IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii

IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii

Glycosylation Analysis of Feline Small Intestine Following Toxoplasma gondii Infection

IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity toToxoplasma gondii

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