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Human Macrophages Encode Stimulus-Specific Information of Prior Exposures Through Trained Immunity

GSE323311 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 48 samples Submitted 2026/03/26 Platform GPL30173
Summary
Trained immunity (a form of innate immune memory), defined in part by heightened responses to pathogen restimulation, can be generated by many different stimuli. However, both the quantitative differences in trained states generated by different stimuli and the downstream consequences of those differences remain unclear. Here, we used primary human monocyte-derived macrophages to demonstrate phenotypic and molecular stimulus specificity of trained immunity six days after initial exposure. Quantification of cytokine production with single-molecule RNA imaging demonstrated stimulus-specific patterns of response to restimulation, with trained cells showed stronger responses to secondary stimuli more similar to their initial stimulation. Differential licensing of inflammatory transcription factors was associated with encoding of specificities in chromatin six days after training, while memory of some, but not all, training stimuli is lost by eleven days post-training in vitro. Overall, our findings demonstrate that different training stimuli can impart specific memories which generate distinct training phenotypes.
Published in
Human macrophages encode stimulus-specific information of prior exposures through trained immunity
O'Farrell A, Niu Z, Li J et al. · Cell systems 2026 · PMID 42320478 · doi:10.1016/j.cels.2026.101647
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Direct links to NCBI, no account and no request form: the whole study as GSE323311_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 48 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1432078 and SRA study SRP681030. Searching any of these in the dataset finder brings you back here.

Study design
20 conditions, mostly in duplicate
Monocyte-derived macrophages from Donor ND410… ×2 Monocyte-derived macrophages from Donor ND410… ×2 Monocyte-derived macrophages from Donor ND410… ×2 Monocyte-derived macrophages from Donor ND410… ×2 Monocyte-derived macrophages from Donor ND650… ×2 Monocyte-derived macrophages from Donor ND650… ×2 Monocyte-derived macrophages from Donor ND650… ×2 Monocyte-derived macrophages from Donor ND650… ×2 +12 more

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