HDAC5 promotes Mycoplasma pneumoniae-induced inflammation in macrophages through NF-κB activation

Area of Science:

• Immunology
• Molecular Biology
• Respiratory Medicine

Background:

• Mycoplasma pneumoniae (MP) infection causes significant respiratory illness in children, driven by excessive inflammation.
• Histone deacetylase 5 (HDAC5) is implicated in inflammatory processes, but its specific role in MP immunity is unknown.

Purpose of the Study:

• To investigate the role of HDAC5 in the immune response to Mycoplasma pneumoniae infection.
• To elucidate the molecular mechanisms by which HDAC5 influences MP-induced inflammation.

Main Methods:

• Analysis of HDAC5 expression in peripheral blood mononuclear cells (PBMCs) from children with Mycoplasma pneumoniae pneumonia (MPP) and in MP-infected macrophages.
• Functional studies involving HDAC5 overexpression and depletion in THP-1 macrophages to assess cytokine production.
• Investigation of HDAC5's effect on NF-κB activation and the impact of NF-κB inhibition on inflammatory responses.

Main Results:

• HDAC5 expression was decreased in PBMCs of MPP patients and in MP-infected macrophages.
• HDAC5 overexpression enhanced, while depletion inhibited, MP-induced proinflammatory cytokine production.
• HDAC5 modulates NF-κB activation in MP-infected macrophages, and NF-κB inhibition reduced HDAC5's pro-inflammatory effect.

Conclusions:

• HDAC5 promotes Mycoplasma pneumoniae-induced inflammatory responses in macrophages via NF-κB activation.
• HDAC5 represents a novel factor in MP pathophysiology and a potential target for controlling inflammation in MPP.