METTL3 Plays Regulatory Roles in Acute Pneumonia during Staphylococcus aureus Infection

Area of Science:

• Molecular Biology
• Immunology
• Pathogen Research

Background:

• Staphylococcus aureus pneumonia causes significant global morbidity and mortality.
• N6-methyladenosine (m6A) modification is implicated in various diseases, but its role in bacterial pneumonia is unclear.

Purpose of the Study:

• To investigate the role of m6A modification in Staphylococcus aureus-induced pneumonia.
• To determine the specific involvement of METTL3 in the host response to S. aureus infection.

Main Methods:

• Assessed m6A levels and expression of key epigenetic regulators (METTL3, METTL14, FTO, YTHDF1, YTHDF2) in infected mice and MH-S cells.
• Utilized METTL3 knockdown (siMETTL3) to evaluate its functional impact.
• Analyzed inflammatory cytokines, bacterial load, lung damage, oxidative stress markers, and signaling pathways (MAPK/NF-κB/JAK2-STAT3, Pink1/Parkin).

Main Results:

• m6A and METTL3 levels were significantly upregulated during S. aureus infection.
• METTL3 knockdown exacerbated bacterial colonization, lung inflammation, cytokine release (IL-6, IL-1β, TNF-α), mortality, and oxidative stress.
• METTL3 regulated inflammation via MAPK/NF-κB/JAK2-STAT3 and protected against impaired mitochondrial autophagy.

Conclusions:

• METTL3 exhibits a protective role against Staphylococcus aureus-induced acute pneumonia.
• METTL3's function involves modulating inflammatory responses and oxidative stress.
• METTL3 represents a potential therapeutic target for S. aureus infections.