Bacterial outer membrane vesicles induce disseminated intravascular coagulation through the caspase-11-gasdermin D pathway

Peng, Yue; Gao, Min; Liu, Yukun; Qiu, Xianhui; Cheng, Xiaoye; Yang, Xinyu; Chen, Fangping; Wang, Erhua

doi:10.1016/j.thromres.2020.08.013

Cited by 27 publications

(21 citation statements)

References 25 publications

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“…The study also determined that extracellular HMGB1-LPS complexes were transported via the plasma membrane advanced glycosylation endproduct specific receptor (AGER, best known as RAGE) into the lysosomes of mouse macrophages and endothelial cells, where HMGB1 destabilized lysosomal membranes and facilitated the release of LPS into the cytosol to activate CASP11 for pyroptosis, thus promoting lethal coagulation (Figure 2) [55]. These findings established a DAMP-dependent pathway for the delivery of LPS into the cytosol, activating CASP11 and coagulation, independently from previously reported non-DAMP pathways through bacteria-released outer membrane vesicles [56] or human guanylate binding protein 1 (GBP1) [57,58]. Thus, transport of LPS into cells is likely to involve multiple pathways and, collectively, these studies highlight the importance of cellsurface as well as cytosolic LPS sensing in promoting cellular pathways that lead to coagulation activation in sepsis.…”

Section: Hmgb1supporting

confidence: 59%

Emerging mechanisms of immunocoagulation in sepsis and septic shock

Tang

Wang

Billiar

et al. 2021

Trends in Immunology

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Section: Hmgb1supporting

confidence: 59%

Emerging mechanisms of immunocoagulation in sepsis and septic shock

Tang

Wang

Billiar

et al. 2021

Trends in Immunology

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“…Challenge with bacterial pathogens may result in the cleavage of GSDMD in animals and cultured cells (15)(16)(17). Although the relationship between the bacterial pathogen that produces CDC and the lysis of the host GSDMD has not been reported, previous studies have shown that pneumolysin (PLY) secreted by Streptococcus pneumoniae can induce caspase-1 activation and IL-1b secretion in murine microglia and neutrophils (18,19).…”

Section: Introductionmentioning

confidence: 99%

Pyolysin of Trueperella pyogenes Induces Pyroptosis and IL-1β Release in Murine Macrophages Through Potassium/NLRP3/Caspase-1/Gasdermin D Pathway

Liang

Wang

et al. 2022

Front. Immunol.

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Trueperella pyogenes (T. pyogenes) is a commensal and an opportunistic pathogen of animals. This organism can cause inflammatory diseases, such as pneumonia, mastitis and endometritis in hosts. However, the molecular basis for the pro-inflammatory properties of this organism is still largely unknown. In the current study, using murine macrophages as model, the ability of T. pyogenes to induce pyroptosis was first determined. Then, pyolysin (PLO), a cholesterol-dependent cytolysin secreted by T. pyogenes, was found to be closely related to T. pyogenes-induced pyroptosis. Next, our work showed that PLO can form pores in the cell membrane, leading to the efflux of potassium (K+), NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated caspase-1 activation, and gasdermin D (GSDMD) cleavage. Inhibition of the K+/NLRP3/caspase-1/GSDMD pathway abolished T. pyogenes and PLO-induced IL-1β release. Taken together, these results indicate T. pyogenes-induced inflammation is related to PLO-induced pyroptosis and IL-1β release. Our work shed light on the pathogenesis of T. pyogenes and the interaction between T. pyogenes and hosts’ immune system.

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“…In addition to free proteins and enzymes, bacteria release MVs that protect their cargo against degradation related to environmental conditions (e.g., pH) or enzymatic actions [62]. Pathogenic bacteria use MVs to transport a broad range of PAMPs and to interact with the host, thereby contributing to disease progression [53,54,63]. According to that, MVs isolated from the supernatant of S. aureus cultures induced a strong response in T-lymphocytes (Figure 1a).…”

Section: Discussionmentioning

confidence: 99%

“…Jurkat cells exposed to the supernatant of strains Newman or Cowan I did not exhibit any changes in phase contrast or cell shape as compared to untreated control cells. Since bacteria release MVs that might play a role in disease progression [53,54], we aimed to investigate the effect of MVs only on T-lymphocytes. Therefore, Jurkat cells were treated with MVs isolated from the supernatant of S. aureus cultures.…”

Section: Strain-dependent Morphological Changes Of Jurkat Cells Expos...mentioning

confidence: 99%

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Investigating Morphological Changes of T-lymphocytes after Exposure with Bacterial Determinants for Early Detection of Septic Conditions

et al. 2022

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Sepsis is a leading cause of morbidity and mortality, annually affecting millions of people worldwide. Immediate treatment initiation is crucial to improve the outcome but despite great progress, early identification of septic patients remains a challenge. Recently, white blood cell morphology was proposed as a new biomarker for sepsis diagnosis. In this proof-of-concept study, we aimed to investigate the effect of different bacteria and their determinants on T-lymphocytes by digital holographic microscopy (DHM). We hypothesize that species- and strain-specific morphological changes occur, which may offer a new approach for early sepsis diagnosis and identification of the causative agent. Jurkat cells as a model system were exposed to different S. aureus or E. coli strains either using sterile determinants or living bacteria. Time-lapse DHM was applied to analyze cellular morphological changes. There were not only living bacteria but also membrane vesicles and sterile culture supernatant-induced changes of cell area, circularity, and mean phase contrast. Interestingly, different cellular responses occurred depending on both the species and strain of the causative bacteria. Our findings suggest that investigation of T-lymphocyte morphology might provide a promising tool for the early identification of bacterial infections and possibly discrimination between different causative agents. Distinguishing gram-positive from gram-negative infection would already offer a great benefit for the proper administration of antibiotics.

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Bacterial outer membrane vesicles induce disseminated intravascular coagulation through the caspase-11-gasdermin D pathway

Cited by 27 publications

References 25 publications

Emerging mechanisms of immunocoagulation in sepsis and septic shock

Emerging mechanisms of immunocoagulation in sepsis and septic shock

Pyolysin of Trueperella pyogenes Induces Pyroptosis and IL-1β Release in Murine Macrophages Through Potassium/NLRP3/Caspase-1/Gasdermin D Pathway

Investigating Morphological Changes of T-lymphocytes after Exposure with Bacterial Determinants for Early Detection of Septic Conditions

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