scholarly journals Type I interferon enhances necroptosis of Salmonella Typhimurium–infected macrophages by impairing antioxidative stress responses

2017 ◽  
Vol 216 (12) ◽  
pp. 4107-4121 ◽  
Author(s):  
Nina Judith Hos ◽  
Raja Ganesan ◽  
Saray Gutiérrez ◽  
Deniz Hos ◽  
Jennifer Klimek ◽  
...  
Keyword(s):  
Cell Death ◽  
Stress Responses ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Type I Interferon ◽  
Redox Homeostasis ◽  
Type I ◽  
Interacting Protein ◽  
Serovar Typhimurium ◽  
Autophagic Degradation ◽  
Antioxidative Stress

Salmonella enterica serovar Typhimurium exploits the host’s type I interferon (IFN-I) response to induce receptor-interacting protein (RIP) kinase–mediated necroptosis in macrophages. However, the events that drive necroptosis execution downstream of IFN-I and RIP signaling remain elusive. In this study, we demonstrate that S. Typhimurium infection causes IFN-I–mediated up-regulation of the mitochondrial phosphatase Pgam5 through RIP3. Pgam5 subsequently interacts with Nrf2, which sequesters Nrf2 in the cytosol, thereby repressing the transcription of Nrf2-dependent antioxidative genes. The impaired ability to respond to S. Typhimurium–induced oxidative stress results in reactive oxygen species–mediated mitochondrial damage, energy depletion, transient induction of autophagy, and autophagic degradation of p62. Reduced p62 levels impair interaction of p62 with Keap1, which further decreases Nrf2 function and antioxidative responses to S. Typhimurium infection, eventually leading to cell death. Collectively, we identify impaired Nrf2-dependent redox homeostasis as an important mechanism that promotes cell death downstream of IFN-I and RIP3 signaling in S. Typhimurium–infected macrophages.

scholarly journals Type I interferon induces necroptosis in macrophages during infection with Salmonella enterica serovar Typhimurium

2012 ◽  
Vol 13 (10) ◽  
pp. 954-962 ◽  
Author(s):  
Nirmal Robinson ◽  
Scott McComb ◽  
Rebecca Mulligan ◽  
Renu Dudani ◽  
Lakshmi Krishnan ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Type I Interferon ◽  
Type I ◽  
Serovar Typhimurium

scholarly journals The STING1 network regulates autophagy and cell death

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Ruoxi Zhang ◽  
Rui Kang ◽  
Daolin Tang
Keyword(s):  
Cell Death ◽  
Mitotic Cell ◽  
Therapeutic Interventions ◽  
Type I Interferons ◽  
Microbial Pathogens ◽  
Type I ◽  
Autophagic Degradation ◽  
Health And Disease ◽  
Shed Light ◽  
Pro Inflammatory Cytokines

AbstractCell death and immune response are at the core of life. In past decades, the endoplasmic reticulum (ER) protein STING1 (also known as STING or TMEM173) was found to play a fundamental role in the production of type I interferons (IFNs) and pro-inflammatory cytokines in response to DNA derived from invading microbial pathogens or damaged hosts by activating multiple transcription factors. In addition to this well-known function in infection, inflammation, and immunity, emerging evidence suggests that the STING1-dependent signaling network is implicated in health and disease by regulating autophagic degradation or various cell death modalities (e.g., apoptosis, necroptosis, pyroptosis, ferroptosis, mitotic cell death, and immunogenic cell death [ICD]). Here, we outline the latest advances in our understanding of the regulating mechanisms and signaling pathways of STING1 in autophagy and cell death, which may shed light on new targets for therapeutic interventions.

scholarly journals Viral RNA Induces Type I Interferon-Dependent Cytokine Release and Cell Death in Mesangial Cells via Melanoma-Differentiation-Associated Gene-5

2009 ◽  
Vol 175 (5) ◽  
pp. 2014-2022 ◽  
Author(s):  
Katharina Flür ◽  
Ramanjaneyulu Allam ◽  
Daniel Zecher ◽  
Onkar P. Kulkarni ◽  
Julia Lichtnekert ◽  
...  
Keyword(s):  
Cell Death ◽  
Mesangial Cells ◽  
Type I Interferon ◽  
Viral Rna ◽  
Type I ◽  
Cytokine Release

scholarly journals Type I interferon signaling is required for activation of the inflammasome during Francisella infection

2007 ◽  
Vol 204 (5) ◽  
pp. 987-994 ◽  
Author(s):  
Thomas Henry ◽  
Anna Brotcke ◽  
David S. Weiss ◽  
Lucinda J. Thompson ◽  
Denise M. Monack
Keyword(s):  
Cell Death ◽  
Type I Interferon ◽  
Infection Type ◽  
Host Responses ◽  
Inflammasome Activation ◽  
Type I ◽  
Type I Ifn ◽  
Caspase 1 ◽  
Dependent Cell

Francisella tularensis is a pathogenic bacterium whose virulence is linked to its ability to replicate within the host cell cytosol. Entry into the macrophage cytosol activates a host-protective multimolecular complex called the inflammasome to release the proinflammatory cytokines interleukin (IL)-1β and -18 and trigger caspase-1–dependent cell death. In this study, we show that cytosolic F. tularensis subspecies novicida (F. novicida) induces a type I interferon (IFN) response that is essential for caspase-1 activation, inflammasome-mediated cell death, and release of IL-1β and -18. Extensive type I IFN–dependent cell death resulting in macrophage depletion occurs in vivo during F. novicida infection. Type I IFN is also necessary for inflammasome activation in response to cytosolic Listeria monocytogenes but not vacuole-localized Salmonella enterica serovar Typhimurium or extracellular adenosine triphosphate. These results show the specific connection between type I IFN signaling and inflammasome activation, which are two sequential events triggered by the recognition of cytosolic bacteria. To our knowledge, this is the first example of the positive regulation of inflammasome activation. This connection underscores the importance of the cytosolic recognition of pathogens and highlights how multiple innate immunity pathways interact before commitment to critical host responses.

scholarly journals Neutrophils infected with highly virulent influenza H3N2 virus exhibit augmented early cell death and rapid induction of type I interferon signaling pathways

Genomics ◽  
2013 ◽  
Vol 101 (2) ◽  
pp. 101-112 ◽  
Author(s):  
Fransiskus X. Ivan ◽  
K.S. Tan ◽  
M.C. Phoon ◽  
Bevin P. Engelward ◽  
Roy E. Welsch ◽  
...  
Keyword(s):  
Cell Death ◽  
Signaling Pathways ◽  
Type I Interferon ◽  
H3n2 Virus ◽  
Type I ◽  
Interferon Signaling ◽  
Rapid Induction ◽  
Influenza H3n2 ◽  
Highly Virulent

scholarly journals Activation of metabolic and stress responses during subtoxic expression of the type I toxin hok in Erwinia amylovora

2021 ◽  
Author(s):  
Jingyu Peng ◽  
Lindsay R. Triplett ◽  
George Sundin
Keyword(s):  
Cell Death ◽  
Stress Responses ◽  
Erwinia Amylovora ◽  
Physiological State ◽  
Fruit Trees ◽  
Toxin Gene ◽  
Type I ◽  
Pome Fruit ◽  
Membrane Rupture ◽  
High Level

Abstract Background: Toxin-antitoxin (TA) systems, abundant in prokaryotes, are composed of a toxin gene and its cognate antitoxin. Several toxins are implied to affect the physiological state and stress tolerance of bacteria in a population. We previously identified a chromosomally encoded hok-sok type I TA system in Erwinia amylovora, the causative agent of fire blight disease on pome fruit trees. A high-level induction of the hok gene was lethal to E. amylovora cells through unknown mechanisms. The molecular targets or regulatory roles of Hok were unknown.Results: Here, we examined the physiological and transcriptomic changes of Erwinia amylovora cells expressing hok at subtoxic levels that were confirmed to confer no cell death, and at toxic levels that resulted in killing of cells. In both conditions, hok caused membrane rupture and collapse of the proton motive force in a subpopulation of E. amylovora cells. We demonstrated that induction of hok resulted in upregulation of ATP biosynthesis genes, and caused leakage of ATP from cells only at toxic levels. We showed that overexpression of the phage shock protein gene pspA largely reversed the cell death phenotype caused by high levels of hok induction. We also showed that induction of hok at a subtoxic level rendered a greater proportion of stationary phase E. amylovora cells tolerant to the antibiotic streptomycin. Conclusions: We characterized the molecular mechanism of toxicity by high-level of hok induction and demonstrated that low-level expression of hok primes the stress responses of E. amylovora against further membrane and antibiotic stressors.

Sign in / Sign up

Export Citation Format

Share Document