Table 1.

Comparison of alterations in innate immune responses during aging (inflammaging) and the absence/reduction in type I IFN [2,131].

Cell Type/Signaling	Aging	Absence/Reduction in Type I IFN
PRR activation & signaling	↑ High age-related basal PRR (TLR) activation leads to excessive pro-inflammatory cytokine production ↓ Post-PRR downstream signaling activation	↓ Recognition of intracellular pathogens ↑ Activity of Nlrp3 inflammasome ↓ ISGs expression signaling ↓Inducible nitric oxide synthase (iNOS)
Neutrophils	↑ Neutrophil influx through IL-17, CXCL1, CXCL2 ↓ Phagocytic function ↓ Signaling pathway	↑ Neutrophil recruitment by CXCL1 and CXCL2 production by monocytes
Monocyte/Macrophages	↑ IL-6 and TNF production ↓ Macrophage phagocytosis of apoptotic neutrophils ↓ Alveolar macrophage affects repair of lung damage	↓ Inflammatory monocyte-derived macrophages (IM) recruitment ↑ Resident IM proliferation ↓ IM iNOS, ↑ Ly6Clo monocyte iNOS production ↓ IM TRAIL expression ↓ Macrophage phagocytosis and efferocytosis of apoptotic neutrophils
NK cells, Type I IFN	↓ Delayed type I IFN activation and production ↓ Cytotoxic early viral clearance ↑ Cytokine production and consequent lung damage ↑ NK cell apoptosis	↓ NK cell activation and IFN-production ↓ NK cell survival
Dendritic cells	↓ Functional capability ↓ DC maturation and migration to lymphoid organs affect T cell activation	↑ cDC2 subtype development ↓ Antiviral responses by lowering ISGs ↓ Migration function

↓: decrease; ↑: increase.