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

摘要

B-cell lymphoma 10(Bcl10) is a scaffolding protein that functions as an upstream regulator of NF-κB signaling by forming a complex with Mucosa-associated lymphoid tissue lymphoma translocation protein 1(Malt1) and CARD-coiled coil protein family. This study showed that Bcl10 was involved in type I interferon(IFN) expression in response to DNA virus infection and that Bcl10-deficient mice were more susceptible to Herpes simplex virus 1(HSV-1) infection than control mice. Mechanistically,DNA virus infection can trigger Bcl10 recruitment to the STING-TBK1 complex, leading to Bcl10 phosphorylation by TBK1.The phosphorylated Bcl10 undergoes droplet-like condensation and forms oligomers, which induce TBK1 phosphorylation and translocation to the perinuclear region. The activated TBK1 phosphorylates IRF3, which induces the expression of type I IFNs.This study elucidates that Bcl10 induces an innate immune response by undergoing droplet-like condensation and participating in signalosome formation downstream of the c GAS-STING pathway.