GEO series

Phagosome-mediated activation of STING by purine and pyrimidine-based bacterial cyclic dinucleotides

GSE331176 Mus musculus Expression profiling by high throughput sequencing 380 samples Submitted 2026/07/17 Platform GPL34290

Summary

The cytoplasm harbors a spectrum of microbial sensory proteins. Beyond pathogens and their membrane disruptive activities, the contexts and mechanisms whereby bacterial molecules access cytoplasmic sensors are unknown. In this study, we describe the intracellular cyclic dinucleotide (CDN) sensor STING from humans, mice, and other animals as a driver of immune responses to a spectrum of CDNs produced by evolutionarily diverse bacteria, including those containing pyrimidine bases. Diverse bacterial CDNs were present in murine tissues and increased in human inflammatory bowel diseases patients. After bacteriolysis in phagolysosomes, bacterial CDNs could activate STING via two CDN transporters. Systemic delivery of dead, CDN-laden bacteria promoted resistance to subcutaneous and liver-localized tumors in mice. X-ray crystallography of STING-CDN complexes revealed distinct binding modes for purine- and pyrimidine-based CDNs. We propose a connection between phagocytosis, bacterial CDNs, and STING that ensures cytoplasmic innate immune responses are a common outcome of host-bacteria interactions.

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Direct links to NCBI, no account and no request form: the whole study as GSE331176_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 380 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1467455 and SRA study SRP701543. Searching any of these in the dataset finder brings you back here.

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Study design

31 conditions, each sampled once — no replicated groups

WT iBMDMs, 4hr time point, untreated, ×2 WT iBMDMs, 4hr time point, clearcoli, ×2 WT iBMDMs, 4hr time point, dacA+, ×2 Cgas-/- iBMDMs, 4hr time point, untreated, ×2 Cgas-/- iBMDMs, 4hr time point, clearcoli, ×2 Cgas-/- iBMDMs, 4hr time point, dacA+, ×2 Sting-/- iBMDMs, 4hr time point, untreated, ×2 Sting-/- iBMDMs, 4hr time point, clearcoli, ×2 +1 more

Read from the first 40 of 380 sample titles: 31 distinct titles with little repetition. Check it against the sample list below before relying on it.

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