The Toxoplasma Effector GRA4 Hijacks Host TBK1 to Oppositely Regulate Anti‐T. Gondii Immunity and Tumor Immunotherapy DOI Creative Commons
Zhiqiang Hu,

Yufen Zhang,

Yingchao Xie

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(32)

Published: June 21, 2024

Abstract Toxoplasma gondii ( T. )‐associated polymorphic effector proteins are crucial in parasite development and regulating host anti‐ immune responses. However, the mechanism remains obscure. Here, it is shown that dense granules 4 (GRA4) restricts IFN‐I activation. Infection with Δ gra4 mutant strain induces stronger responses poses a severe threat to health. Mechanistically, GRA4 binds phosphorylated TBK1 promote TRIM27‐catalyzed K48‐ubiquitination at Lys251/Lys372 residues, which enhances its recognition by autophagy receptor p62, ultimately leading autophagic degradation. Furthermore, an avirulent (ME49Δ ompdc / ) constructed for tumor immunotherapy due ability enhance production. Earlier vaccination ME49Δ confers complete resistance compared classical treatment. Notably, specific CD64 + MAR‐1 CD11b dendritic cell subset, thereby enhancing T anti‐tumor Overall, these findings identify negative role of modulating signaling suggest can be potential target vaccines immunotherapy.

Language: Английский

The Toxoplasma Effector GRA4 Hijacks Host TBK1 to Oppositely Regulate Anti‐T. Gondii Immunity and Tumor Immunotherapy DOI Creative Commons
Zhiqiang Hu,

Yufen Zhang,

Yingchao Xie

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(32)

Published: June 21, 2024

Abstract Toxoplasma gondii ( T. )‐associated polymorphic effector proteins are crucial in parasite development and regulating host anti‐ immune responses. However, the mechanism remains obscure. Here, it is shown that dense granules 4 (GRA4) restricts IFN‐I activation. Infection with Δ gra4 mutant strain induces stronger responses poses a severe threat to health. Mechanistically, GRA4 binds phosphorylated TBK1 promote TRIM27‐catalyzed K48‐ubiquitination at Lys251/Lys372 residues, which enhances its recognition by autophagy receptor p62, ultimately leading autophagic degradation. Furthermore, an avirulent (ME49Δ ompdc / ) constructed for tumor immunotherapy due ability enhance production. Earlier vaccination ME49Δ confers complete resistance compared classical treatment. Notably, specific CD64 + MAR‐1 CD11b dendritic cell subset, thereby enhancing T anti‐tumor Overall, these findings identify negative role of modulating signaling suggest can be potential target vaccines immunotherapy.

Language: Английский

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