Group A Streptococcus induces GSDMA-dependent pyroptosis in keratinocytes

LaRock, Doris L.; Johnson, Anders F.; Wilde, Shyra; Sands, Jenna S.; Monteiro, Marcos P

doi:10.1038/s41586-022-04717-x

Cited by 102 publications

(82 citation statements)

References 37 publications

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“…Many studies on non-apoptotic regulated cell death (RCD) in tumor immunotherapy, including autophagy, ferroptosis, pyroptosis, and necroptosis, highlights the importance of research on non-apoptotic cell death mechanisms, and also indicate that these complex interactions can flow into several core molecular mechanisms [97]. Various microbial pathogen components and autoinflammatory factors also trigger these core molecular mechanisms, such as the CASP family/Granzyme-GSDM family axis and SLC7A11-GPX4 axis [98]. For example, Talaromyces marneffei can activate pyroptosis mediated by AIM2-caspase-1/-4-GSDMD in hepatocytes [99].…”

Section: Discussionmentioning

confidence: 99%

Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level

Zhang

et al. 2022

J Transl Med

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Background Approximately 8–9% of the world’s population is affected by autoimmune diseases, and yet the mechanism of autoimmunity trigger is largely understudied. Two unique cell death modalities, ferroptosis and pyroptosis, provide a new perspective on the mechanisms leading to autoimmune diseases, and development of new treatment strategies. Methods Using scRNA-seq datasets, the aberrant trend of ferroptosis and pyroptosis-related genes were analyzed in several representative autoimmune diseases (psoriasis, atopic dermatitis, vitiligo, multiple sclerosis, systemic sclerosis-associated interstitial lung disease, Crohn’s disease, and experimental autoimmune orchitis). Cell line models were also assessed using bulk RNA-seq and qPCR. Results A substantial difference was observed between normal and autoimmune disease samples involving ferroptosis and pyroptosis. In the present study, ferroptosis and pyroptosis showed an imbalance in different keratinocyte lineages of psoriatic skinin addition to a unique pyroptosis-sensitive keratinocyte subset in atopic dermatitis (AD) skin. The results also revealed that pyroptosis and ferroptosis are involved in epidermal melanocyte destruction in vitiligo. Aberrant ferroptosis has been detected in multiple sclerosis, systemic sclerosis-associated interstitial lung disease, Crohn’s disease, and autoimmune orchitis. Cell line models adopted in the study also identified pro-inflammatory factors that can drive changes in ferroptosis and pyroptosis. Conclusion These results provide a unique perspective on the involvement of ferroptosis and pyroptosis in the pathological process of autoimmune diseases at the scRNA-seq level. IFN-γ is a critical inducer of pyroptosis sensitivity, and has been identified in two cell line models.

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Section: Discussionmentioning

confidence: 99%

Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level

Zhang

et al. 2022

J Transl Med

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“…Additionally, GZMB may promote pyroptosis by either directly cleaving GSDME at the same site or indirectly activating caspase‐3 to cleave GSDME 59 . Recent studies find that Streptococcus pyogenes , often known as group A Streptococcus (GAS), secretes a protease virulence factor called SpeB, which cleaves GSDMA after Gln246 to release the N‐terminal fragment that induces pyroptosis 60,61 …”

Section: Mechanisms Of Pyroptosismentioning

confidence: 99%

Pyroptosis in inflammatory bone diseases: Molecular insights and targeting strategies

2022

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Inflammatory bone diseases include osteoarthritis (OA) and rheumatoid arthritis (RA), which can cause severe bone damage in a chronic inflammation state, putting tremendous pressure on the patients' families and government agencies regarding medical costs. In addition, the complexity of osteoimmunology makes research on these diseases difficult. Hence, it is urgent to determine the potential mechanisms and find effective drugs to target inflammatory bone diseases to reduce the negative effects of these diseases. Recently, pyroptosis, a gasdermininduced necrotic cell death featuring secretion of pro-inflammatory cytokines and lysis, has become widely known. Based on the effect of pyroptosis on immunity, this process has gradually emerged as a vital component in the etiopathogenesis of inflammatory bone diseases. Herein, we review the characteristics and mechanisms of pyroptosis and then focus on its clinical significance in inflammatory How to cite this article: Zhang R-N, Sun Z-J, Zhang L. Pyroptosis in inflammatory bone diseases: Molecular insights and targeting strategies. The

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“…In addition to GSDMD, the N-terminal domains released from granzyme A-cleaved GSDMB, caspase 8-cleaved GSDMC or granzyme B/caspase 3-cleaved GSDME have also been shown to mediate pyroptosis [ 25 , 32 , 33 , 34 , 35 , 36 ]. GSDMA has recently been reported to be cleaved by a protease virulence factor, SpeB, released by human pathogen group A Streptococcus [ 37 ].…”

Section: An Overview Of Programmed Necrosismentioning

confidence: 99%

The Role of Programmed Necrosis in Colorectal Cancer

Gámez‐Belmonte

Patankar

et al. 2022

Cancers

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For quite a long time, necrosis was considered a chaotic and unorganized form of cell death. However, studies conducted during the past few decades unveiled multiple types of programmed necrosis, such as necroptosis, pyroptosis and ferroptosis. These types of programmed necrosis have been shown to play crucial roles in mediating pathological processes, including tumorigenesis. Almost all key mediators, such as RIPK3 and MLKL in necroptosis, GSDMD and caspase 1/11 in pyroptosis and GPX4 in ferroptosis, are highly expressed in intestinal epithelial cells (IECs). An aberrant increase or decrease in programmed necrosis in IECs has been connected to intestinal disorders. Here, we review the pathways of programmed necrosis and the specific consequences of regulated necrosis in colorectal cancer (CRC) development. Translational aspects of programmed necrosis induction as a novel therapeutic alternative against CRC are also discussed.

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Group A Streptococcus induces GSDMA-dependent pyroptosis in keratinocytes

Cited by 102 publications

References 37 publications

Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level

Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level

Pyroptosis in inflammatory bone diseases: Molecular insights and targeting strategies

The Role of Programmed Necrosis in Colorectal Cancer

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