α-Toxin Induces Platelet Aggregation and Liver Injury during Staphylococcus aureus Sepsis

Cell Host & Microbe
Bas G J SurewaardPaul 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.

Citations

Feb 19, 2019·Journal of Leukocyte Biology·Brittney N V ScottAjitha Thanabalasuriar
Mar 23, 2019·Blood·Fernanda V S Castanheira, Paul Kubes
Aug 30, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zhanguo LiuPeng Chen
Aug 25, 2018·Blood·Craig N Jenne
May 23, 2020·International Journal of Environmental Research and Public Health·Renin ChangChih-Hsin Hung
May 29, 2020·Antioxidants & Redox Signaling·Viktoria Rungelrath, Frank R DeLeo
Oct 23, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andreas Margraf, Alexander Zarbock
Jan 28, 2020·Platelets·Olivia Susanto, Michael J Hickey
Nov 30, 2018·Medical Microbiology and Immunology·Vigyasa Singh, Ujjal Jyoti Phukan
Sep 24, 2019·The Journal of Clinical Investigation·Selina K JorchPaul Kubes
Aug 18, 2020·Journal of Inflammation Research·Anna LichotaEligia M Szewczyk
Jan 29, 2019·European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery·Kota SuzukiYoshiki Sawa
Jul 19, 2019·Frontiers in Immunology·Fabrice CognasseHind Hamzeh-Cognasse
Nov 22, 2019·Frontiers in Immunology·Nonantzin Beristain-CovarrubiasAdam F Cunningham
Apr 16, 2019·The Journal of Clinical Investigation·Taylor S CohenBret R Sellman
Nov 5, 2019·Frontiers in Medicine·Nadji HannachiLaurence Camoin-Jau
Apr 9, 2020·Frontiers in Microbiology·Clovis Macêdo Bezerra FilhoMaria Luiza Vilela Oliva
Jun 26, 2020·Frontiers in Pharmacology·Nadji HannachiLaurence Camoin-Jau
Sep 9, 2020·Platelets·Kimberly Martinod, Carsten Deppermann
Oct 13, 2020·Frontiers in Immunology·Lu Li, Zhutian Zeng
Aug 19, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Guanqiao LiuBin Yu
Mar 2, 2021·Frontiers in Cell and Developmental Biology·Selina K Jorch, Carsten Deppermann
Apr 6, 2021·Frontiers in Cellular and Infection Microbiology·Zhaoyuan ChenChanghong Miao
Apr 22, 2020·Developmental Cell·Elena PanizzaMarc A Antonyak
Feb 20, 2021·Canadian Journal of Microbiology·Celine Stoica, Georgina Cox
Jul 30, 2021·Scientific Reports·Josefien W HommesBas G J Surewaard
Nov 9, 2019·Journal of Agricultural and Food Chemistry·Shuai-Cheng WuJian-Zhong Shen
Jan 15, 2020·ACS Applied Materials & Interfaces·Jianghua LiMary B Chan-Park

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