Table 1 The major components of STING pathway

cGAS

An evolutionarily conserved cytosolic DNA sensor

It uses ATP and GTP as substrates to catalyze the synthesis of cGAMP

cGAMP

A cyclic dinucleotide second messenger

It binds to STING localized on the ER membrane, which promotes STING oligomerization and translocation from the ER to the Golgi apparatus

STING

An ER membrane protein as a key adaptor in innate immunity,

Its oligomerization recruits TBK1 and further triggers IRF3- and NF-κB-dependent transcription of type I IFNs

TBK1

A serine/threonine kinase

It phosphorylates STING and subsequently activates both IRF3 and NF-κB

IRF3

A transcription regulator

After phosphorylated by TBK1, it subsequently translocates to the nucleus, where it induces the transcription of inflammatory factors

NF-κB

A transcription regulator

After activated byTBK1 and IκB kinase epsilon, it synergizes with IRF3 to induce the transcription of inflammatory factors

Type I IFNs

Major downstream molecules (IFN-α and IFN-β) of STING pathway

IFN-α and IFN-β involve in host innate immune activation

Other proinflammatory factors

Inflammatory cytokines (such as TNF, IL-6 and IL-12) and chemokines (such as CXCL9 and CXCL10)

The STING activation is also required for the induction of many other genes encodings proinflammatory factors that regulates both innate and adaptive immunity