ROP16 of <i>Toxoplasma gondii</i> Inhibits Innate Immunity by Triggering cGAS-STING Pathway Inactivity through the Polyubiquitination of STING
cGAS-STING signaling is a major pathway in inducing type Ⅰ IFN, which plays a crucial role in the defense against <i>T. gondii</i> infection. In contrast, <i>T. gondii</i> develops multiple strategies to counteract the host defense, causing serious diseases in a wide range of...
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MDPI AG
2023-07-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/14/1862 |
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| author | Qi-Wang Jin Ting Yu Ming Pan Yi-Min Fan Si-Yang Huang |
| author_facet | Qi-Wang Jin Ting Yu Ming Pan Yi-Min Fan Si-Yang Huang |
| author_sort | Qi-Wang Jin |
| collection | DOAJ |
| description | cGAS-STING signaling is a major pathway in inducing type Ⅰ IFN, which plays a crucial role in the defense against <i>T. gondii</i> infection. In contrast, <i>T. gondii</i> develops multiple strategies to counteract the host defense, causing serious diseases in a wide range of hosts. Here, we demonstrate that <i>T. gondii</i> rhoptry protein 16 (ROP16) dampens type I interferon signaling via the inhibition of the cGAS (cyclic GMP-AMP synthase) pathway through the polyubiquitination of STING. Mechanistically, ROP16 interacts with STING through the SignalP domain and inhibits the K63-linked ubiquitination of STING in an NLS (nuclear localization signal)-domain-dependent manner. Consequently, knocking out the ROP16 in PRU tachyzoites promotes the STING-mediated production of type I IFNs and limits the replication of <i>T. gondii.</i> Together, these findings describe a distinct pathway where <i>T. gondii</i> exploits the ubiquitination of STING to evade host anti-parasite immunity, revealing new insights into the interaction between the host and parasites. |
| first_indexed | 2024-03-11T01:12:27Z |
| format | Article |
| id | doaj.art-3913d32c87da4d9ca3c4706dc9945e91 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T01:12:27Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj.art-3913d32c87da4d9ca3c4706dc9945e912023-11-18T18:46:14ZengMDPI AGCells2073-44092023-07-011214186210.3390/cells12141862ROP16 of <i>Toxoplasma gondii</i> Inhibits Innate Immunity by Triggering cGAS-STING Pathway Inactivity through the Polyubiquitination of STINGQi-Wang Jin0Ting Yu1Ming Pan2Yi-Min Fan3Si-Yang Huang4Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaJiangsu Key Laboratory of Zoonosis, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaJiangsu Key Laboratory of Zoonosis, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaJiangsu Key Laboratory of Zoonosis, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaJiangsu Key Laboratory of Zoonosis, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinacGAS-STING signaling is a major pathway in inducing type Ⅰ IFN, which plays a crucial role in the defense against <i>T. gondii</i> infection. In contrast, <i>T. gondii</i> develops multiple strategies to counteract the host defense, causing serious diseases in a wide range of hosts. Here, we demonstrate that <i>T. gondii</i> rhoptry protein 16 (ROP16) dampens type I interferon signaling via the inhibition of the cGAS (cyclic GMP-AMP synthase) pathway through the polyubiquitination of STING. Mechanistically, ROP16 interacts with STING through the SignalP domain and inhibits the K63-linked ubiquitination of STING in an NLS (nuclear localization signal)-domain-dependent manner. Consequently, knocking out the ROP16 in PRU tachyzoites promotes the STING-mediated production of type I IFNs and limits the replication of <i>T. gondii.</i> Together, these findings describe a distinct pathway where <i>T. gondii</i> exploits the ubiquitination of STING to evade host anti-parasite immunity, revealing new insights into the interaction between the host and parasites.https://www.mdpi.com/2073-4409/12/14/1862<i>Toxoplasma gondii</i>ROP16cGAS-STING pathwayimmune escape |
| spellingShingle | Qi-Wang Jin Ting Yu Ming Pan Yi-Min Fan Si-Yang Huang ROP16 of <i>Toxoplasma gondii</i> Inhibits Innate Immunity by Triggering cGAS-STING Pathway Inactivity through the Polyubiquitination of STING Cells <i>Toxoplasma gondii</i> ROP16 cGAS-STING pathway immune escape |
| title | ROP16 of <i>Toxoplasma gondii</i> Inhibits Innate Immunity by Triggering cGAS-STING Pathway Inactivity through the Polyubiquitination of STING |
| title_full | ROP16 of <i>Toxoplasma gondii</i> Inhibits Innate Immunity by Triggering cGAS-STING Pathway Inactivity through the Polyubiquitination of STING |
| title_fullStr | ROP16 of <i>Toxoplasma gondii</i> Inhibits Innate Immunity by Triggering cGAS-STING Pathway Inactivity through the Polyubiquitination of STING |
| title_full_unstemmed | ROP16 of <i>Toxoplasma gondii</i> Inhibits Innate Immunity by Triggering cGAS-STING Pathway Inactivity through the Polyubiquitination of STING |
| title_short | ROP16 of <i>Toxoplasma gondii</i> Inhibits Innate Immunity by Triggering cGAS-STING Pathway Inactivity through the Polyubiquitination of STING |
| title_sort | rop16 of i toxoplasma gondii i inhibits innate immunity by triggering cgas sting pathway inactivity through the polyubiquitination of sting |
| topic | <i>Toxoplasma gondii</i> ROP16 cGAS-STING pathway immune escape |
| url | https://www.mdpi.com/2073-4409/12/14/1862 |
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