Systemic inflammation impairs myelopoiesis and interferon type I responses in humans.

Summary

Using a controlled human LPS endotoxemia model spanning both hyperinflammatory and immunosuppressive phases, the authors show that systemic inflammation impairs myelopoiesis and type I interferon responses. Single-cell RNA-seq identified an inflammatory CD163+ population during the acute phase, providing mechanistic insights into human immunoparalysis.

Key Findings

• Controlled human LPS model captured both hyperinflammatory and late immunosuppressive phases of systemic inflammation.
• Single-cell RNA-seq during the acute phase identified an inflammatory CD163+ population.
• Systemic inflammation impaired myelopoiesis and type I interferon responses in humans.

Clinical Implications

Findings support patient stratification and timing of immunotherapies in conditions such as sepsis and acute respiratory distress syndrome by identifying impaired myelopoiesis and type I IFN signaling as key axes.

Limitations

• Abstract provides limited quantitative details on sample size and demographics
• Endotoxemia model may not capture full complexity of clinical sepsis or ARDS

Future Directions

Validate identified cellular programs in patients with sepsis/ARDS, link to outcomes, and test immunomodulatory interventions targeting myelopoiesis and IFN-I pathways.