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. 2025 Jul 8:15:1628481.
doi: 10.3389/fcimb.2025.1628481. eCollection 2025.

The cGAS-STING signaling pathway in the regulation of pulmonary infections: a systematic review

Qinchao Xu  1 , Jiayu Zhu  1
Affiliations

The cGAS-STING signaling pathway in the regulation of pulmonary infections: a systematic review

Qinchao Xu et al. Front Cell Infect Microbiol. .

Abstract

The lungs are constantly exposed to airborne pathogens and depend on robust innate immune surveillance for protection. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway, a core component of the innate immune system, plays a pivotal role in defending against respiratory infections caused by viruses, bacteria, and mycobacteria, including Mycobacterium tuberculosis. Dysregulation of this pathway has been linked to several chronic lung diseases, such as cystic fibrosis, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, and asthma. Upon sensing cytoplasmic DNA, cGAS activates the STING pathway, producing type I interferons and pro-inflammatory cytokines that drive host immune response. However, many pathogens have developed strategies to evade detection or surpass cGAS-STING signaling. This systematic review highlights the molecular mechanisms governing cGAS-STING activation, its interaction with lung pathogens, and its potential as a therapeutic agent in respiratory diseases.

Keywords: cGAS-SING; immune escape; innate immune; lung infection; type I interferons.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Activation of the cGAS-STING signaling pathway in response to cytosolic DNA. cGAS recognizes dsDNA in the cytoplasm and catalyze cGAMP. Subsequently, cGAMP binds to and activates STING, and promotes its transport from ER to Golgi apparatus, STING initiates downstream signaling cascades by activating TBK1-IRF3 and NF-κB pathway.
See this image and copyright information in PMC

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