Journal
CELL HOST & MICROBE
Volume 24, Issue 2, Pages 271-+Publisher
CELL PRESS
DOI: 10.1016/j.chom.2018.06.017
Keywords
-
Categories
Funding
- Canadian Institutes of Health Research (CIHR), CIHR fellowship, Marie Curie Action FP7-PEOPLE-IOF [627575]
- Heart and Stroke Foundation of Canada
Ask authors/readers for more resources
During sepsis, small blood vessels can become occludedby large plateletaggregates of poorly understood etiology. During Staphylococcal aureus infection, sepsis severity is linked to the bacterial a-toxin (a-hemolysin, AT) through unclear mechanisms. In this study, we visualized intravascular events in the microcirculation and found that intravenous AT injection induces rapid platelet aggregation, forming dynamic micro-thrombi in the microcirculation. These aggregates are retained in the liver sinusoids and kidney glomeruli, causing multi-organ dysfunction. Acute staphylococcal infection results in sequestration of most bacteria by liver macrophages. Platelets are initially recruited to these macrophages and help eradicate S. aureus. However, at later time points, AT causes aberrant and damaging thrombosis throughout the liver. Treatment with an AT neutralizing antibody (MEDI4893*) prevents platelet aggregation and subsequent liver damage, without affecting the initial and beneficial platelet recruitment. Thus, AT neutralization may represent a promising approach to combat staphylococcal-induced intravascular coagulation and organ dysfunction.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available