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α-Toxin Induces Platelet Aggregation and Liver Injury during Staphylococcus aureus Sepsis.
- Source :
-
Cell host & microbe [Cell Host Microbe] 2018 Aug 08; Vol. 24 (2), pp. 271-284.e3. Date of Electronic Publication: 2018 Jul 19. - Publication Year :
- 2018
-
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 <superscript>∗</superscript> ) 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.<br /> (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- ADAM10 Protein genetics
ADAM10 Protein metabolism
Amyloid Precursor Protein Secretases genetics
Amyloid Precursor Protein Secretases metabolism
Animals
Antibodies, Monoclonal pharmacology
Antibodies, Monoclonal, Humanized
Antibodies, Neutralizing pharmacology
Bacterial Toxins immunology
Broadly Neutralizing Antibodies
Hemolysin Proteins immunology
Host-Pathogen Interactions physiology
Humans
Intravital Microscopy methods
Liver drug effects
Liver microbiology
Male
Membrane Proteins genetics
Membrane Proteins metabolism
Mice, Inbred C57BL
Mice, Mutant Strains
Platelet Aggregation physiology
Staphylococcus aureus pathogenicity
Bacteremia physiopathology
Bacterial Toxins toxicity
Hemolysin Proteins toxicity
Liver pathology
Platelet Aggregation drug effects
Staphylococcal Infections physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1934-6069
- Volume :
- 24
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell host & microbe
- Publication Type :
- Academic Journal
- Accession number :
- 30033122
- Full Text :
- https://doi.org/10.1016/j.chom.2018.06.017