Title |
α-Toxin Induces Platelet Aggregation and Liver Injury during Staphylococcus aureus Sepsis
|
---|---|
Published in |
Cell Host & Microbe (Science Direct), July 2018
|
DOI | 10.1016/j.chom.2018.06.017 |
Pubmed ID | |
Authors |
Bas G.J. Surewaard, Ajitha Thanabalasuriar, Zhutian Zeng, Christine Tkaczyk, Taylor S. Cohen, Bart W. Bardoel, Selina K. Jorch, Carsten Deppermann, Juliane Bubeck Wardenburg, Rachelle P. Davis, Craig N. Jenne, Kendall C. Stover, Bret R. Sellman, Paul Kubes |
Abstract |
During sepsis, small blood vessels can become occluded by large platelet aggregates of poorly understood etiology. During Staphylococcal aureus infection, sepsis severity is linked to the bacterial α-toxin (α-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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 14 | 29% |
Canada | 4 | 8% |
United Kingdom | 4 | 8% |
Germany | 3 | 6% |
Australia | 2 | 4% |
France | 2 | 4% |
Thailand | 1 | 2% |
Hungary | 1 | 2% |
Mexico | 1 | 2% |
Other | 3 | 6% |
Unknown | 13 | 27% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 25 | 52% |
Scientists | 19 | 40% |
Science communicators (journalists, bloggers, editors) | 2 | 4% |
Practitioners (doctors, other healthcare professionals) | 2 | 4% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 155 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 28 | 18% |
Student > Bachelor | 22 | 14% |
Researcher | 18 | 12% |
Student > Master | 18 | 12% |
Professor | 6 | 4% |
Other | 19 | 12% |
Unknown | 44 | 28% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 31 | 20% |
Biochemistry, Genetics and Molecular Biology | 26 | 17% |
Agricultural and Biological Sciences | 18 | 12% |
Medicine and Dentistry | 12 | 8% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 2% |
Other | 16 | 10% |
Unknown | 49 | 32% |