Tian, X.; Liu, Y.; Zhu, K.; An, H.; Feng, J.; Zhang, L.; Zhang, J.-R.

The interception of blood-borne bacteria in the liver defines the outcomes of invasive bacterial infections, but the mechanisms of this anti-bacterial immunity are largely speculative. This study shows that natural antibodies (nAbs) to capsules enable liver macrophage Kupffer cells (KCs) to rapidly capture and kill blood-borne encapsulated bacteria in mice. Affinity pulldown with serotype-10A capsular polysaccharides (CPS10A) of S. pneumoniae (Spn10A) led to the identification of CPS10A-binding nAbs in serum. The CPS10A-antibody interaction enabled KCs to capture Spn10A bacteria from the bloodstream, in part through complement receptors on KCs. The nAbs were found to recognize the {beta}1-6-linked galactose branch of CPS10A, and similar moieties of serotype-39 S. pneumoniae and serotype-K50 Klebsiella pneumoniae capsules. More importantly, the nAbs empowered KCs to capture serotype-39 S. pneumoniae and serotype-K50 K. pneumoniae in the liver. Collectively, our data have revealed a highly effective immune function of nAb against encapsulated bacteria, and provided a proof of concept for treating septic bacterial diseases with monoclonal antibodies.