scholarly journals Pyroptosis in the Initiation and Progression of Atherosclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhengtao Qian ◽  
Yilin Zhao ◽  
Chuandan Wan ◽  
Yimai Deng ◽  
Yaoyao Zhuang ◽  
...  
Keyword(s):  
Pore Formation ◽  
Innate Immune ◽  
Cell Swelling ◽  
Tumor Resistance ◽  
Immune Effector ◽  
Caspase 1 ◽  
Innate Immune Effector ◽  
Human Caspase ◽  
Progression Of Atherosclerosis

Pyroptosis, a newly discovered form of programmed cell death, is characterized by cell swelling, the protrusion of large bubbles from the plasma membrane and cell lysis. This death pathway is mediated by the pore formation of gasdermin D (GSDMD), which is activated by human caspase-1/caspase-4/caspase-5 (or mouse caspase-1/caspase11), and followed with the releasing of both cell contents and proinflammatory cytokines. Pyroptosis was initially found to function as an innate immune effector mechanism to facilitate host defense against pathogenic microorganisms, and subsequent studies revealed that pyroptosis also plays an eventful role in inflammatory immune diseases and tumor resistance. Recent studies have also shown that pyroptosis is involved in the initiation, the progression and complications of atherosclerosis. Here, we provide an overview of the role of pyroptosis in atherosclerosis by focusing on three important participating cells: ECs, macrophages, and SMCs. In addition, we also summarized drugs and stimuli that regulate the progression of atherosclerosis by influencing cell pyroptosis.

scholarly journals Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria

2010 ◽  
Vol 11 (12) ◽  
pp. 1136-1142 ◽  
Author(s):  
Edward A Miao ◽  
Irina A Leaf ◽  
Piper M Treuting ◽  
Dat P Mao ◽  
Monica Dors ◽  
...  
Keyword(s):  
Innate Immune ◽  
Intracellular Bacteria ◽  
Immune Effector ◽  
Effector Mechanism ◽  
Caspase 1 ◽  
Innate Immune Effector

scholarly journals Type I IFN exacerbates disease in tuberculosis-susceptible mice by inducing neutrophil-mediated lung inflammation and NETosis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Lúcia Moreira-Teixeira ◽  
Philippa J. Stimpson ◽  
Evangelos Stavropoulos ◽  
Sabelo Hadebe ◽  
Probir Chakravarty ◽  
...  
Keyword(s):  
Disease Severity ◽  
Innate Immune ◽  
Neutrophil Extracellular Trap ◽  
Type I ◽  
Type I Ifn ◽  
Immune Effector ◽  
Gm Csf ◽  
Innate Immune Effector ◽  
Important Cytokine

Abstract Tuberculosis (TB) is a leading cause of mortality due to infectious disease, but the factors determining disease progression are unclear. Transcriptional signatures associated with type I IFN signalling and neutrophilic inflammation were shown to correlate with disease severity in mouse models of TB. Here we show that similar transcriptional signatures correlate with increased bacterial loads and exacerbate pathology during Mycobacterium tuberculosis infection upon GM-CSF blockade. Loss of GM-CSF signalling or genetic susceptibility to TB (C3HeB/FeJ mice) result in type I IFN-induced neutrophil extracellular trap (NET) formation that promotes bacterial growth and promotes disease severity. Consistently, NETs are present in necrotic lung lesions of TB patients responding poorly to antibiotic therapy, supporting the role of NETs in a late stage of TB pathogenesis. Our findings reveal an important cytokine-based innate immune effector network with a central role in determining the outcome of M. tuberculosis infection.

scholarly journals Defensins at the Mucosal Surface: Latest Insights into Defensin-Virus Interactions

2016 ◽  
Vol 90 (11) ◽  
pp. 5216-5218 ◽  
Author(s):  
Sarah S. Wilson ◽  
Mayim E. Wiens ◽  
Mayumi K. Holly ◽  
Jason G. Smith
Keyword(s):  
Cell Culture ◽  
Viral Pathogenesis ◽  
Innate Immune ◽  
Immune Effector ◽  
Mucosal Surfaces ◽  
Innate Immune Effector ◽  
Virus Interactions

Defensins are innate immune effector peptides expressed at mucosal surfaces throughout the human body and are potently antiviralin vitro. The role of defensins in viral pathogenesisin vivois poorly understood; however, recent studies have revealed that defensin-virus interactionsin vivoare complicated and distinct from their proposed antiviral mechanismsin vitro. These findings highlight the need for additional research that connects defensin neutralization of viruses in cell culture toin vivoantiviral mechanisms.

scholarly journals The mystery behind membrane insertion: a review of the complement membrane attack complex

2017 ◽  
Vol 372 (1726) ◽  
pp. 20160221 ◽  
Author(s):  
Charles Bayly-Jones ◽  
Doryen Bubeck ◽  
Michelle A. Dunstone
Keyword(s):  
Electron Microscopy ◽  
Structural Biology ◽  
Pore Formation ◽  
Membrane Attack Complex ◽  
Innate Immune ◽  
Membrane Insertion ◽  
Immune Effector ◽  
Membrane Pores ◽  
Cryo Electron Microscopy ◽  
Innate Immune Effector

The membrane attack complex (MAC) is an important innate immune effector of the complement terminal pathway that forms cytotoxic pores on the surface of microbes. Despite many years of research, MAC structure and mechanism of action have remained elusive, relying heavily on modelling and inference from biochemical experiments. Recent advances in structural biology, specifically cryo-electron microscopy, have provided new insights into the molecular mechanism of MAC assembly. Its unique ‘split-washer’ shape, coupled with an irregular giant β-barrel architecture, enable an atypical mechanism of hole punching and represent a novel system for which to study pore formation. This review will introduce the complement terminal pathway that leads to formation of the MAC. Moreover, it will discuss how structures of the pore and component proteins underpin a mechanism for MAC function, modulation and inhibition. This article is part of the themed issue ‘Membrane pores: from structure and assembly, to medicine and technology’.

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