Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell-Morell receptor

Sepsis occurs in the presence of a pathogen in the blood, often with increased blood clotting and inflammation that can cause severe tissue damage and organ failure leading to death. This article reports the mechanism of host protection mediated by the Ashwell-Morell receptor (AMR) of hepatocytes during sepsis caused by Streptococcus pneumoniae. The AMR protects the host primarily by diminishing the abundance of circulating platelets that have been remodeled by pathogen neuraminidase activity, thereby reducing the severity of coagulopathy, diminishing organ failure, and permitting host survival. The AMR is further selective in moderating circulating coagulation factors that are primarily prothrombotic. This study also presents an approach to preactivate AMR function early in sepsis to augment host protection and survival.