Targeting mTOR in myeloid cells prevents infection-associated inflammation.

Summary

Single-cell transcriptomics in COVID-19 identified myeloid mTOR signaling as a key regulator of hyperinflammation. A myeloid-targeted mTOR-inhibiting nanobiologic efficiently homes to myeloid cells and progenitors, and targeting this pathway prevents infection-associated inflammation.

Key Findings

• Single-cell RNA-seq of circulating immune cells in COVID-19 patients implicates myeloid mTOR signaling as a critical regulator of hyperinflammation.
• An mTOR-inhibiting nanobiologic efficiently targets myeloid cells and their progenitors in the bone marrow.
• Targeting mTOR in myeloid cells prevents infection-associated inflammation (as per study title), indicating a tractable therapeutic pathway.

Clinical Implications

Suggests a therapeutic avenue to modulate dysregulated innate immunity in infection-associated ARDS by targeting myeloid mTOR; supports development of trials evaluating safety, timing, and dosing of myeloid-directed mTOR inhibition.

Limitations

• Abstract does not detail clinical outcomes; translational efficacy in ARDS patients remains to be established.
• Preclinical stage with safety, dosing, and durability yet to be evaluated in humans.

Future Directions

Test myeloid-targeted mTOR inhibition across sepsis/ARDS models; define therapeutic window, biomarkers of response, and safety in early-phase clinical trials.