miR-155 aggravates inflammation in MRSA pneumonia by modulating macrophage polarization.

BACKGROUND

Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is a severe infection with high mortality, where alveolar macrophages (AMs) play a critical role in host defense through M1 polarization. MicroRNA-155 (miR-155) is known to modulate immune responses, but its specific role in AM polarization during MRSA pneumonia remains unclear. This study investigates how miR-155 regulates M1 macrophage polarization and MRSA pneumonia.

METHODS

The experiments were performed in both vitro and in miR-155 knockout mice. The activity of miR-155 and polarization of AMs were evaluated using scanning electron microscopy, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Lung pathology, inflammatory markers, and potential signaling pathways (particularly AKT/mTOR) were analyzed.

RESULTS

miR-155 expression was significantly upregualted in MRSA infection, while miR-155 promoted M1 macrophage polarization as demonstrated by distinct morphological changes, elevated CD86 levels, and increased IL-6 production. miR-155 deficiency attenuated this response, reducing inflammatory cytokine release and lung pathology while impairing AKT/mTOR pathway activation, indicating that miR-155 exacerbates MRSA-induced pneumonia by driving M1 polarization through AKT/mTOR signaling.

CONCLUSIONS

Our findings reveal that miR-155 modulates M1 macrophage polarization and aggrevates MRSA-induced pneumonia by activating the AKT/mTOR pathway. This study provides new insights into host-pathogen interactions in MRSA infection, suggesting miR-155 as a potential therapeutic target.