Rapamycin Exacerbates Staphylococcus aureus Pneumonia by Inhibiting mTOR-RPS6 in Macrophages

Area of Science:

• Immunology
• Microbiology
• Pharmacology

Background:

• Staphylococcus aureus (S. aureus) is a common cause of bacterial pneumonia.
• Rapamycin (Rapa) is an immunosuppressant drug with potential immunomodulatory effects.
• The role of Rapa in S. aureus pneumonia requires further elucidation.

Purpose of the Study:

• To investigate the effect of Rapamycin (Rapa) on Staphylococcus aureus (S. aureus) pneumonia.
• To clarify the underlying mechanisms of Rapa's action in S. aureus pneumonia.

Main Methods:

• S. aureus pneumonia mouse models and in vitro macrophage cultures were used.
• Investigated mTOR-RPS6 pathway phosphorylation and phagocytosis.
• Utilized myeloid cell-specific Mtor knockout mice for in vivo validation.

Main Results:

• Rapa exacerbated S. aureus pneumonia, increasing chemokine secretion and inflammatory cell infiltration.
• In vitro, Rapa upregulated macrophage chemokine and cytokine secretion.
• mTOR-RPS6 pathway inhibition increased inflammation; Rapa did not enhance phagocytosis.

Conclusions:

• Rapamycin exacerbates S. aureus pneumonia by amplifying macrophage inflammatory responses.
• Inhibition of the mTOR-RPS6 pathway promotes inflammation, worsening S. aureus pneumonia severity and tissue damage.