Endoplasmic Reticulum Stress in Immunity

Bettigole, Sarah E.; Glimcher, Laurie H.

doi:10.1146/annurev-immunol-032414-112116

Cited by 398 publications

(352 citation statements)

References 212 publications

(185 reference statements)

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“…Proteotoxic damage responses are aimed at repairing or eventually degrading unfolded nascent or mature proteins as a means to preserve essential cellular functions 53,54 . Proteotoxic damage responses can act as bona fide tissue damage control mechanisms, promoting the establishment of disease tolerance to bacterial infection 53,[55][56][57][58] ( Figure 2). Of note, proteotoxic damage responses are also involved in the regulation of immune-driven resistance mechanisms against intracellular bacteria and viruses, some of which evolved to modulate these responses as a strategy to repress host resistance to infection 53 59 .…”

Section: Damage Responses and Tissue Damage Controlmentioning

confidence: 99%

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Disease tolerance and immunity in host protection against infection

2017

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The immune system has most likely evolved to limit the negative impact exerted by pathogens on host homeostasis. This defense strategy relies on the concerted action of innate and adaptive components of the immune system, which sense and target pathogens for containment, destruction or expulsion. Resistance to infection refers to these immune functions, which reduce the pathogen load of an infected host as the means to preserve homeostasis. Immune-driven resistance to infection is coupled to an additional, and arguably as important, defense strategy that limits the extent of dysfunction imposed to host parenchyma tissues during infection, without exerting a direct negative impact on pathogens.This defense strategy, called disease tolerance, relies on tissue damage control mechanisms that prevent the deleterious effects of pathogens, while uncoupling immunedriven resistance mechanisms from immunopathology and disease. Here we provide a unifying view of resistance and disease tolerance within the framework of immunity to infection.

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Section: Damage Responses and Tissue Damage Controlmentioning

confidence: 99%

“…aeruginosa infection in C. elegans 58 while preserving homeostatic control of microbiota interactions with host gut epithelia 53 . The DNA damage responses orchestrated by ATM 17 and by p53 165 confer tissue damage control and disease tolerance to pulmonary bacterial infections in mice.…”

Section: Box 3 Microbiota and Disease Tolerancementioning

confidence: 99%

Disease tolerance and immunity in host protection against infection

2017

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“…[5][6][7][8][9][10] In addition to the induction of IFNs, viral infections also trigger ER stress response. [11][12][13][14][15] A best-studied stress-responsive signaling pathway is the UPR. The UPR induces transmembrane stress sensors, IRE1, ATF6, and PERK, that are localized in the ER.…”

Section: Introductionmentioning

confidence: 99%

Integrated Stress Response Signaling Pathways Induced by Supraphysiological Concentrations of Thyroid Hormone Inhibit Viral Replication

Ishaq

Natarajan

2016

Signal Transduction Insights

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Supraphysiological concentrations (SPCs) of triiodo-l-thyronine (T3) have been used in the treatment of a number of nonviral diseases. However, the signaling mechanisms that regulate the function of T3 at these concentrations and their role in modulating cellular stress pathways and antiviral responses are unknown. Here, we have investigated the effects of SPCs of T3 on integrated stress response (ISR) signaling pathways and the replication of vesicular stomatitis virus (VSV). T3 amplified Poly IC-induced activation of RNA-dependent protein kinase, induced phosphorylation of eIF2α, stress granule (SG) formation, IRE1α phosphorylation, XBP1 splicing, and the expression of stress markers. T3 inhibited VSV replication by modulating SG formation and the expression of stress response markers. ISR activator guanabenz also inhibited VSV replication and amplified T3-induced anti-VSV response. To summarize, we have uncovered novel functions of T3 at SPCs as an activator of ISR signaling pathways and an inhibitor of VSV replication. This study offers a proof of principle of the concept that ISR activating agents like SPC of T3 and guanabenz can be potential antiviral agents.

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“…One of them is initiated by protein kinase RNA-like ER kinase (PERK). Activation of PERK contributes to the accumulation of activating transcription factor 4 (ATF4) (Bettigole and Glimcher, 2015;Sano and Reed, 2013), which upregulates ATF3 and CHOP expression. We checked the expression level of the CHOP-encoding gene ddit3 and found that, like atf3, ddit3 was upregulated in zar1 mutants (Fig.…”

Section: Loss Of Zar1 Triggers Er Stress and The Unfolded Protein Resmentioning

confidence: 99%

Translation repression by maternal RNA binding protein zar1 is essential for early oogenesis in zebrafish

et al. 2016

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A large amount of maternal RNA is deposited in oocytes and is reserved for later development. Control of maternal RNA translation during oocyte maturation has been extensively investigated and its regulatory mechanisms are well documented. However, translational regulation of maternal RNA in early oogenesis is largely unexplored. In this study, we generated zebrafish zar1 mutants that result in early oocyte apoptosis and fully penetrant male development. Loss of p53 suppresses the apoptosis in zar1 mutants and restores oocyte development. zar1 immature ovaries show upregulation of proteins implicated in endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). More importantly, loss of Zar1 causes marked upregulation of zona pellucida (ZP) family proteins, while overexpression of ZP proteins in oocytes causes upregulation of stress-related activating transcription factor 3 (atf3), arguing that tightly controlled translation of ZP proteins is essential for ER homeostasis during early oogenesis. Furthermore, Zar1 binds to ZP gene mRNAs and represses their translation. Together, our results indicate that regulation of translational repression and de-repression are essential for precisely controlling protein expression during early oogenesis.

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Endoplasmic Reticulum Stress in Immunity

Cited by 398 publications

References 212 publications

Disease tolerance and immunity in host protection against infection

Disease tolerance and immunity in host protection against infection

Integrated Stress Response Signaling Pathways Induced by Supraphysiological Concentrations of Thyroid Hormone Inhibit Viral Replication

Translation repression by maternal RNA binding protein zar1 is essential for early oogenesis in zebrafish

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