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

Summary

Using a controlled human LPS endotoxemia model, the authors mapped both hyperinflammatory and subsequent immunosuppressive phases. Single-cell RNA sequencing identified an inflammatory CD163+ population, and the study demonstrates that systemic inflammation impairs myelopoiesis and type I interferon responses in humans.

Key Findings

• A controlled human LPS-induced systemic inflammation model captured both hyperinflammatory and immunosuppressive phases.
• Single-cell RNA sequencing during the acute phase identified an inflammatory CD163+ population.
• Systemic inflammation impairs myelopoiesis and type I interferon responses in humans.

Clinical Implications

Identifying impaired myelopoiesis and type I IFN pathways may enable phase-specific biomarkers and targeted immunomodulation to mitigate post-inflammatory immunosuppression.

Limitations

• Endotoxemia may not fully recapitulate pathogen-driven clinical sepsis
• Generalizability to diverse patient populations with comorbidities is uncertain

Future Directions

Validate findings in patients with sepsis of infectious etiology, develop biomarkers of phase transition, and test therapies restoring myelopoiesis and type I IFN pathways.