To understand how the liver executes the clearance of blood-borne bacteria, we sought to identify the receptor(s) recognizing the capsule of serotype-23F S. pneumoniae (Sp23F), one of the most predominant serotypes causing the childhood invasive infection. Our previous study has shown that Sp23F is rapidly captured by KCs into the liver of mice (Low virulence,LV). Our initial experiment showed that the hepatic immunity is blocked by free capsular polysaccharide of Sp23F (CPS23F). Consistently, the freshly isolated KCs from mouse liver showed significant adherence to LV Sp23F with normal mouse serum, but were poorly adherent to high virulence (HV) Sp8. We enriched CPS23F-binding protein(s) by affinity pulldown after incubation of CPS23F-coated beads with the membrane protein-enriched fraction of mouse liver nonparenchymal cells (NPCs) in the presence of 10% mouse serum. CPS of the HV serotype-8 S. pneumoniae (CPS8) was used as a negative control due to its poor binding to KCs