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Quantifying stimulus-response specificity to probe the functional state of macrophages
Katherine M Sheu1, Aditya A Guru1, Alexander Hoffmann1
1Department of Microbiology, Immunology, and Molecular Genetics, and Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, 611 Charles E. Young Dr S, Los Angeles, CA 90093, USA.
Researchers quantified stimulus-response specificity (SRS) in immune cells. Macrophage SRS, driven by specific gene combinations, reflects their functional state and can be altered by cytokines, offering insights into innate immunity.
Area of Science:
- Immunology
- Systems Biology
- Computational Biology
Background:
- Immune sentinel macrophages orchestrate pathogen defense using numerous immune response genes.
- Tailored responses to diverse immune threats highlight the importance of stimulus-specific gene expression in macrophages.
Purpose of the Study:
- To quantify stimulus-response specificity (SRS) in macrophages.
- To develop a single-cell workflow and analytical methods for measuring SRS.
- To assess how SRS reflects macrophage functional state and is affected by age and obesity.
Main Methods:
- Developed a single-cell experimental workflow.
- Applied information theory and machine learning for data analysis.
- Analyzed stimulus-response distributions and response specificity profiles.
Main Results:
- Identified that macrophage SRS is driven by specific immune genes with low cell-to-cell heterogeneity and distinct signaling pathways.
- Demonstrated that polarizing cytokines distinctly alter the response specificity profile.
- Observed characteristic differences in the SRS profile of peritoneal macrophages from old and obese mice.
Conclusions:
- Stimulus-response specificity (SRS) is a key functional hallmark of healthy macrophages.
- The response specificity profile serves as a measure of macrophage functional state.
- SRS analysis provides a basis for assessing the functional status of innate immune cells, particularly in conditions like aging and obesity.
