The Salmonella effector SopB prevents ROS-induced apoptosis of epithelial cells by retarding TRAF6 recruitment to mitochondria

Ruan, Haihua; Zhang, Zhen; Tian, Li; Wang, Suying; Hu, Shuangyan; Qiao, Jianjun

doi:10.1016/j.bbrc.2016.07.116

Cited by 35 publications

(22 citation statements)

References 32 publications

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“…Abnormal ROS production promotes inflammation and inflammatory programmed cell death 16,22 . TNFR‐associated factors (TRAFs) are important mediators of inflammatory reactions signaling 26,39 and ROS regulation 40 . TRAF6 regulates TLR‐stimulated MAPKs and NF‐κB activation and is considered important for ROS‐dependent activation of innate immune pathways 41 .…”

Section: Discussionmentioning

confidence: 99%

TRAF3 promotes ROS production and pyroptosis by targeting ULK1 ubiquitination in macrophages

et al. 2020

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oxygen species; TLR, toll-like receptor; TRAF3, tumor necrosis factor receptorassociated factor 3; ULK1, Unc-51 like autophagy activating kinase 1. AbstractDisrupted mitochondrial function and reactive oxygen species (ROS) generation cause cellular damage and oxidative stress-induced macrophage inflammatory cell death. It remains unclear how mitochondrial dysfunction relates to inflammasome activation and pyroptotic cell death. In this study, we demonstrated that tumor necrosis factor receptor-associated factor 3 (TRAF3) regulates mitochondrial ROS production and promotes TLR agonist LPS plus nigericin (LPS/Ng)-induced inflammasome and pyroptosis in mouse primary macrophages and human monocyte THP-1 cells. Co-IP assays confirmed that TRAF3 forms a complex with TRAF2 and cIAP1 and mediates ubiquitin and degradation of Unc-51 like autophagy activating kinase 1 (ULK1). Moreover, knockdown of ULK1 in THP-1 cells significantly promoted LPS/Ng-induced inflammasome by activating caspase 1 and mature IL-1β. Apoptosis inducing factor (AIF) translocation from mitochondrial to nuclear was observed in ULK1-deficient THP-1 cells under LPS/Ng stimulation, which mediates LPS/Ng-induced cell death in ULK1 deficient macrophages. In conclusion, this study identified a novel role of TRAF3 in regulation of ULK1 ubiquitination and inflammasome signaling and provided molecular mechanisms by which ubiquitination of ULK1 controls mitochondrial ROS production, inflammasome activity, and AIF-dependent pyroptosis. K E Y W O R D S cell death, inflammasome, macrophages, mitochondrial, reactive oxygen species | 7145 SHEN Et al.

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Section: Discussionmentioning

confidence: 99%

TRAF3 promotes ROS production and pyroptosis by targeting ULK1 ubiquitination in macrophages

et al. 2020

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“…Enhanced epithelial apoptosis and increased mortality were noted in the absence of SopB, consistent with a recent report that demonstrated protection from Nlrc4/ASC-mediated apoptosis by SopB in vitro [ 20 , 83 ]. SopB might additionally prevent apoptosis by other mechanisms [ 21 , 84 ]. Epithelial barrier damage after infection with Δ sopB Salmonella explains the higher bacterial load in the mesenteric lymph node.…”

Section: Discussionmentioning

confidence: 99%

Minimal SPI1-T3SS effector requirement for Salmonella enterocyte invasion and intracellular proliferation in vivo

et al. 2018

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Effector molecules translocated by the Salmonella pathogenicity island (SPI)1-encoded type 3 secretion system (T3SS) critically contribute to the pathogenesis of human Salmonella infection. They facilitate internalization by non-phagocytic enterocytes rendering the intestinal epithelium an entry site for infection. Their function in vivo has remained ill-defined due to the lack of a suitable animal model that allows visualization of intraepithelial Salmonella. Here, we took advantage of our novel neonatal mouse model and analyzed various bacterial mutants and reporter strains as well as gene deficient mice. Our results demonstrate the critical but redundant role of SopE2 and SipA for enterocyte invasion, prerequisite for transcriptional stimulation and mucosal translocation in vivo. In contrast, the generation of a replicative intraepithelial endosomal compartment required the cooperative action of SipA and SopE2 or SipA and SopB but was independent of SopA or host MyD88 signaling. Intraepithelial growth had no critical influence on systemic spread. Our results define the role of SPI1-T3SS effector molecules during enterocyte invasion and intraepithelial proliferation in vivo providing novel insight in the early course of Salmonella infection.

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“…The SopB effector protein of Salmonella typhimurium suppresses mROS generation in response to infection to dampen the host immune response and to facilitate its establishment into the host cell [60]. SopB binds to cytosolic tumor necrosis factor receptor associated factor 6 (TRAF6), prevents its recruitment to mitochondria and inhibits apoptosis [60].…”

Section: Mitochondrial Dynamics During Bacterial Infectionmentioning

confidence: 99%

The Role of Mitochondria in Inflammation: From Cancer to Neurodegenerative Disorders

Missiroli

Genovese

Perrone

et al. 2020

JCM

174

124

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The main features that are commonly attributed to mitochondria consist of the regulation of cell proliferation, ATP generation, cell death and metabolism. However, recent scientific advances reveal that the intrinsic dynamicity of the mitochondrial compartment also plays a central role in proinflammatory signaling, identifying these organelles as a central platform for the control of innate immunity and the inflammatory response. Thus, mitochondrial dysfunctions have been related to severe chronic inflammatory disorders. Strategies aimed at reestablishing normal mitochondrial physiology could represent both preventive and therapeutic interventions for various pathologies related to exacerbated inflammation. Here, we explore the current understanding of the intricate interplay between mitochondria and the innate immune response in specific inflammatory diseases, such as neurological disorders and cancer.

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The Salmonella effector SopB prevents ROS-induced apoptosis of epithelial cells by retarding TRAF6 recruitment to mitochondria

Cited by 35 publications

References 32 publications

TRAF3 promotes ROS production and pyroptosis by targeting ULK1 ubiquitination in macrophages

TRAF3 promotes ROS production and pyroptosis by targeting ULK1 ubiquitination in macrophages

Minimal SPI1-T3SS effector requirement for Salmonella enterocyte invasion and intracellular proliferation in vivo

The Role of Mitochondria in Inflammation: From Cancer to Neurodegenerative Disorders

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