Bcl10 phosphorylation-dependent droplet-like condensation positively regulates DNA virus-induced innate immune

Dandan Yang1, Gaofeng Pei2,3, Shuangshuang Dong2,3

  • 1Institute for Immunology, School of Medicine, Tsinghua University, Beijing, 100084, China.

Science China. Life Sciences
|September 17, 2022
PubMed

Insights

B-cell lymphoma 10 (Bcl10) protein is crucial for innate immunity against DNA viruses. Bcl10 forms condensates, activating the STING-TBK1 pathway to boost type I interferon production and antiviral defense.

Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • B-cell lymphoma 10 (Bcl10) is a key regulator of NF-κB signaling.
  • The role of Bcl10 in antiviral innate immunity requires further elucidation.

Purpose of the Study:

  • To investigate the function of Bcl10 in type I interferon (IFN) expression during DNA virus infection.
  • To elucidate the molecular mechanisms by which Bcl10 regulates the innate immune response to viral pathogens.

Main Methods:

  • Utilized Bcl10-deficient mice to assess susceptibility to Herpes simplex virus 1 (HSV-1) infection.
  • Investigated the recruitment and phosphorylation of Bcl10 within the STING-TBK1 signaling complex.
  • Analyzed Bcl10-dependent formation of protein condensates and signalosomes.

Main Results:

  • Bcl10-deficient mice exhibited increased susceptibility to HSV-1 infection.
  • DNA virus infection induced Bcl10 recruitment to the STING-TBK1 complex, leading to its phosphorylation by TBK1.
  • Phosphorylated Bcl10 formed droplet-like condensates, promoting TBK1 activation and subsequent IRF3 phosphorylation for type I IFN production.

Conclusions:

  • Bcl10 plays a critical role in antiviral innate immunity by regulating type I IFN expression.
  • Bcl10 induces an innate immune response through droplet-like condensation and signalosome formation downstream of the cGAS-STING pathway.

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