Deficiency of protease-activated receptor-1 limits bacterial dissemination during severe Gram-negative sepsis (melioidosis).
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.
Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Center for Experimental and Molecular Medicine, Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: l.m.kager@amc.uva.nl.
Liesbeth M
LM
Kager
Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Center for Experimental and Molecular Medicine, Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Division of Infectious Diseases, Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
W Joost
WJ
Wiersinga
Department of Pathology, Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Joris J T H
JJ
Roelofs
Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Center for Experimental and Molecular Medicine, Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Cornelis
C
van 't Veer
Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Center for Experimental and Molecular Medicine, Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Division of Infectious Diseases, Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Tom
T
van der Poll
D000818:Animals; D016957:Burkholderia pseudomallei / Q000254:growth & development / Q000302:isolation & purification; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions; D008297:Male; D008554:Melioidosis / Q000382:microbiology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044463:Receptor, PAR-1 / Q000172:deficiency* / Q000378:metabolism*; D018805:Sepsis / Q000382:microbiology* / Q000473:pathology*; D016019:Survival Analysis
D044463:Receptor, PAR-1
Lung inflammation; Melioidosis; Pneumonia; Protease-activated receptor-1; Sepsis