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

PRABHJIT GREWAL; AZIZ PV; UCHIYAMA S; RUBIO G; LARDONE RICARDO D; LE DZUNG; VARKI NISSI ; DITTO D; MARTH JAMEY D

NATL ACAD SCIENCES

Lugar: Washington DC, USA; Año: 2013 vol. 110 p. 20218 - 20218

he endocytic Ashwell-Morell receptor (AMR) of hepatocytes detects pathogen remodeling of host glycoproteins by neuraminidase in the bloodstream and mitigates the lethal coagulopathy of sepsis. We have investigated the mechanism of host protection by the AMR during the onset of sepsis and in response to the desialylation of blood glycoproteins by the NanA neuraminidase of Streptococcus pneumoniae. We find that the AMR selects among potential glycoprotein ligands unmasked by microbial neuraminidase activity in pneumococcal sepsis to eliminate from blood circulation host factors that contribute to coagulation and thrombosis. This protection is attributable in large part to the rapid induction of a moderate thrombocytopenia by the AMR. We further show that neuraminidase activ