Fig. 5: CD47 neutralization enhances protection against super-infection.

For neutralization test, 6–8-weeks-old (18–21 g of body weight) C57BL/6 WT mice were infected with 10 PFU of influenza virus on day 0 and 5 × 105 CFU of S. aureus on day 7. Before bacterial infection, mice were intranasally treated twice at day 5 and 7 with IgG2a control antibodies (2A3, n = 17) or α-mCD47 neutralizing antibodies (MIAP301, n = 16). a, b Body weight loss (a) and survival rates (b) were monitored for 29 days. The dotted line indicates the body weight exclusion cut-off. A mantel cox survival analysis was used to compare the survival rates between groups. The numbers in parenthesis are numbers of survived mice. c Representative hematoxylin and eosin (H&E) staining of lung sections (IgG2a + Mock, n = 4; α-mCD47 Ab + Mock, n = 4; IgG2a + Virus only, n = 7; α-mCD47 Ab + Virus only, n = 7; IgG2a + Bacteria only, n = 4; α-mCD47 Ab + Bacteria only, n = 4; IgG2a + Super-infection, n = 9; α-mCD47 Ab + Super-infection, n = 11). The dotted lines indicate lymphocytic infiltration and arrows indicate alveolar hemorrhage. Lung injury scores are presented as violin plots. d–j Tissue injury parameters were measured at 24 h after bacterial infection (IgG2a + Mock, n = 4; α-mCD47 Ab + Mock, n = 4; IgG2a + Virus only, n = 7; α-mCD47 Ab + Virus only, n = 7; IgG2a + Bacteria only, n = 4; α-mCD47 Ab + Bacteria only, n = 4; IgG2a + Super-infection, n = 7-9; α-mCD47 Ab + Super-infection, n = 7-11); total cell number in BAL fluids (BALF) (d), bacterial adherence (e) and invasion (f) in the lung, and the bacterial burden in the spleen (g), total protein concentrations (h) in BALF, and inflammatory cytokines TNF-α (i) and IL-6 (j) in BALF. Data are presented as mean values ± SEM. Significance was determined by unpaired two-tailed t test. n.s. not significant. N.D. not determined. Source data are provided as a Source Data file.