Targeting mTOR in myeloid cells prevents infection-associated inflammation

Area of Science:

• Immunology
• Nanomedicine
• Molecular Biology

Background:

• Life-threatening hyperinflammation can arise from infections, cancer, and trauma.
• The mammalian target of rapamycin (mTOR) pathway is implicated in myeloid cell regulation, particularly in COVID-19 patients.

Purpose of the Study:

• To investigate the role of the mTOR pathway in myeloid cell regulation during hyperinflammation.
• To evaluate the therapeutic potential of an mTOR-inhibiting nanobiologic (mTORi-nanobiologic) in preclinical models of hyperinflammation and acute respiratory distress syndrome.

Main Methods:

• Single-cell RNA sequencing of circulating immune cells.
• In vitro studies using human primary immune cells.
• In vivo studies in mouse models of hyperinflammation and acute respiratory distress syndrome, utilizing 18F-FDG uptake and flow cytometry.

Main Results:

• The mTOR pathway critically regulates myeloid cells in COVID-19 patients.
• mTORi-nanobiologics potently inhibit infection-associated inflammation in vitro.
• In vivo, mTORi-nanobiologic therapy significantly reduced hematopoietic organ metabolic activity and inflammation in mouse models.

Conclusions:

• Targeting myelopoiesis with mTORi-nanobiologics is a promising strategy to mitigate organ inflammation in infection-related complications.
• mTORi-nanobiologics demonstrate efficacy in reducing inflammation and metabolic activity in preclinical models of hyperinflammation.