Deficiency of protease-activated receptor-1 limits bacterial dissemination during severe Gram-negative sepsis (melioidosis).

Abstract

Protease-activated receptor-1 (PAR-1) is a G-coupled transmembrane receptor expressed by multiple cell types present in the lungs that can be activated by various proteases generated during acute inflammation. In this study we aimed to investigate the role of PAR-1 during melioidosis, a common cause of (pneumo)sepsis in Southeast Asia in a murine model of intranasal inoculation of the causative pathogen Burkholderia (B.) pseudomallei. Our results show that endogenous PAR-1 facilitates bacterial growth and dissemination during murine melioidosis, which is associated with increased cell influxes. However, these observations have no impact on survival.