Mitochondrial function in aging plasmacytoid dendritic cells and its role in type I interferon responses 3813

Abstract Description The vulnerability of older adults to severe viral infections and cancers highlights the importance of understanding immunosenescence, a process of age-related immune dysfunction. Older individuals have lower percentages of type I interferon (IFN-I) producing plasmacytoid dendritic cells (pDC) compared to younger individuals (p = 0.008). These cells are critical for antiviral immunity and are the most potent producers of IFN-I in response to viral stimulation. To investigate this decline, we examined how mitochondrial health, particularly mitochondrial reactive oxygen species (mtROS) and mitochondrial membrane potential (MMP), differ in pDC between younger (20s) and older (60+) individuals. Our results show pDC from older individuals exhibit lower mtROS expression and MMP levels than younger donors, both at baseline and following influenza A (IAV) stimulation. While stimulation increased mtROS in younger donors, no increase occurred in older donors. MMP differences between age groups were also seen in mock and stimulated conditions, with MMP trending downward after stimulation. To examine the role of mtROS in IFN-I production, we used Antimycin A, a mitochondrial complex III inhibitor. Early mtROS induction inhibited IFN-I production, while later mtROS induction enhanced it. These findings suggest that age-related mitochondrial changes, marked by altered mtROS and MMP, impair pDC IFN-I responses and highlight the importance of mitochondrial dynamics in pDC senescence. Topic Categories Viral Immunology (VIR)