Heightened cholesterol 25-hydroxylase expression in aged lung during Streptococcus pneumoniae

Alveolar macrophages (AM) are critical effectors of the immune response and are essential for host responses to . Changes in lipid metabolism in AM can alter cellular function and biology. Impaired metabolism can contribute to excessive lipid accumulation and pro-inflammatory signaling. Our current study was designed to examine the role of cholesterol 25-hydroxylase (Ch25h), a redox enzyme that catalyzes the oxidation of cholesterol to 25-hydroxycholesterol (25-HC), in modulating AM responses in the aged lung during infection. To observe the impact of aging on Ch25h expression AM during infection, and murine models of were used. At baseline and in response to infection, cholesterol metabolism significantly altered in aged AM, which corresponded with increased lipid droplet formation. treatment of aged macrophages with Ch25 h-specific siRNA improved clearance and enhanced phagocytic receptor expression. siRNA targeting significantly reduced Ch25h expression in aged lungs and improved clinical parameters during infection. Reduction of Ch25h was associated with changes in phagocytosis and antibacterial signaling, correlated with changes in cholesterol metabolism, and increased clearance. The results of our current study demonstrate that Ch25h plays an essential role in modulating aged AM responses to .