The importance of C3 and C3 receptors in nAb -mediated pneumococcal capture. (A) Bacteremia kinetics of antibody receptor-deficient mice i.v. infected with 10⁶ CFU of TH860^10A. n = 6. (B) Flow cytometry detection of C3 deposition on TH860^10A surface after incubation with serum from μMT or WT mice. (C) Bacteremia kinetics of C1qa^−/− and C3^−/− mice infected as in A. n = 6. (D) Representative IVM images of liver sinusoids (left) and quantitation of bacteria immobilized on KCs (right) of C1qa^−/− and C3^−/− mice i.v. infected with 5 × 10⁷ CFU of TH860^10A. n = 2. The clearance processes are demonstrated in Video 6. (E) Survival rates of WT, C1qa^−/−, or C3^−/− mice i.v. infected with 10⁸ CFU of TH860^10A. n = 10. (F) Bacteremia kinetics of C3-receptor-deficient mice infected as in A. n = 6. (G and H) Representative IVM images of liver sinusoids (G) and quantitation of bacteria immobilized on KCs (H) of C3-receptor-deficient mice i.v. infected with 5 × 10⁷ CFU of TH860^10A. Scale bar, 10 μm. n = 2. The clearance processes are demonstrated in Video 7. (I) Survival of C3- and C3-receptor-deficient mice i.v. infected with 10⁸ CFU of TH860^10A. n = 10. (J and K) Bacteremia kinetics (J) and bacterial distribution at 30 min (K) of C5^−/− and C9^−/− mice infected as in (A). n = 6. (L) Working model of nAbs in driving hepatic clearance of encapsulated bacteria. Invading bacteria in the blood are bound by nAbs, which subsequently activates the complement system. C3 opsonzid bacteria are captured by C3 receptors CR3 and CRIg on KCs. Data were representative results (B, D, G, and H) or pooled from two independent experiments (A, C, E, F, and I–K). Ordinary two-way ANOVA with Tukey’s multiple comparisons test (A, C, F, and J), one-way ANOVA with Tukey’s multiple comparisons test (D and H), and log-rank test (E and I) were performed. *, P < 0.05; **, P < 0.01; ****, P < 0.0001; ns, not significant.