NEIL2 ensures optimal host fitness without collateral tissue injury.Neil2+/+ and Neil2−/− mice were intranasally infected with RSV (106 PFU per mouse) for the indicated time. A, total cell and differential cell counts in the BALF are expressed as the number of cells per milliliter. Data are mean ± SD, n = 6 from three biological replicates, two-sided, unpaired Student’s t test. B, representative images of infiltrate cells in BALF. Arrows indicate macrophages. The scale bar represents 50 μm in lower magnification, and 20 μm with zoom in. C, representative H&E staining of lung sections. The scale bar represents 100 μm in lower magnification, and 50 μm with zoom in. D, total cellular-infiltrates, and neutrophil numbers in BALF at day 1 p.i. Neil2+/+ and Neil2−/− mice were transfected with heat-inactivated (HI) or activate (Act) rNEIL2 prior to RSV-infection. Data are mean ± SD, n = 5 from three biological replicates, two-sided, unpaired Student’s t test. E, representative H&E staining of lung sections from Neil2−/− mice transfected with heat-inactivated (HI) and activate (Act) rNEIL2. The scale bar represents 100 μm in lower magnification, and 50 μm with zoom in. F, Western blot shows the protein levels of NEIL2, OGG1 and MTH1 in the lungs of Neil2+/+ mice at indicated days p.i (dpi). Blot is from six mice per group pooled from three biological replicates. G, body weight in Neil2+/+ and Neil2−/− mice at indicated days p.i. H, body weight in Neil2+/+ and Neil2−/− mice supplemented heat-inactivated (HI) and activate (Act) rNEIL2 at indicated days p.i. G and H, data are mean ± SD, n = 6 from three biological replicates, two-way ANOVA, ∗∗∗p < 0.001.