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Moretti, J., Roy, S., Bozec, D., Martinez, J., Chapman, J. R., & Ueberheide, B., et al. (2022). Sting senses microbial viability to orchestrate stress-mediated autophagy of the endoplasmic reticulum. Cell, 171(4), 809–823.e13. Added by: Dr. Enrique Feoli (22/07/2022, 12:19) Last edited by: Dr. Enrique Feoli (14/11/2022, 20:12) |
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| Resource type: Journal Article ID no. (ISBN etc.): 0092-8674 BibTeX citation key: Moretti2022 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Constitutive innate immunity Creators: Blander, Bozec, Chapman, Chen, Green, Horng, Lamming, Martinez, Moretti, Roy, Ueberheide, Yeretssian Collection: Cell |
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| Abstract |
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Constitutive cell-autonomous immunity in metazoans predates interferon-inducible immunity and comprises primordial innate defense. Phagocytes mobilize interferon-inducible responses upon engagement of well-characterized signaling pathways by pathogen-associated molecular patterns (PAMPs). The signals controlling deployment of constitutive cell-autonomous responses during infection have remained elusive. Vita-PAMPs denote microbial viability, signaling the danger of cellular exploitation by intracellular pathogens. We show that cyclic-di-adenosine monophosphate in live Gram-positive bacteria is a vita-PAMP, engaging the innate sensor stimulator of interferon genes (STING) to mediate endoplasmic reticulum (ER) stress. Subsequent inactivation of the mechanistic target of rapamycin mobilizes autophagy, which sequesters stressed ER membranes, resolves ER stress, and curtails phagocyte death. This vita-PAMP-induced ER-phagy additionally orchestrates an interferon response by localizing ER-resident STING to autophagosomes. Our findings identify stress-mediated ER-phagy as a cell-autonomous response mobilized by STING-dependent sensing of a specific vita-PAMP and elucidate how innate receptors engage multilayered homeostatic mechanisms to promote immunity and survival after infection.}, ={10.1016/j.cell.2017.09.034, doi: 10.1016/j.cell.2017.09.034
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| Notes |
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doi: 10.1016/j.cell.2017.09.034, Constitutive cell-autonomous immunity in metazoans predates interferon-inducible immunity and comprises primordial innate defense. Phagocytes mobilize interferon-inducible responses upon engagement of well-characterized signaling pathways by pathogen-associated molecular patterns (PAMPs). The signals controlling deployment of constitutive cell-autonomous responses during infection have remained elusive. Vita-PAMPs denote microbial viability, signaling the danger of cellular exploitation by intracellular pathogens. We show that cyclic-di-adenosine monophosphate in live Gram-positive bacteria is a vita-PAMP, engaging the innate sensor stimulator of interferon genes (STING) to mediate endoplasmic reticulum (ER) stress. Subsequent inactivation of the mechanistic target of rapamycin mobilizes autophagy, which sequesters stressed ER membranes, resolves ER stress, and curtails phagocyte death. This vita-PAMP-induced ER-phagy additionally orchestrates an interferon response by localizing ER-resident STING to autophagosomes. Our findings identify stress-mediated ER-phagy as a cell-autonomous response mobilized by STING-dependent sensing of a specific vita-PAMP and elucidate how innate receptors engage multilayered homeostatic mechanisms to promote immunity and survival after infection.
Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |
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Added by: Dr. Enrique Feoli
(2022-11-14 19:54:33)
Comments:
STING engagement disrupts ER homeostasis and serves as a previously unappreciated mechanism of mobilizing a constitutive cell-autonomous integrated stress response to live Gram-positive bacteria. This stress response is crucial for initiating an appropriate innate immune response and maintaining cell homeostasis in response to bacterial infection. Unlike the classic PAMPs shared between live and dead microorganisms, vita-PAMPs in this context serve a prominent and indispensable role in triggering these responses because they signify the viability of the microorganism and the associated heightened threat to the integrity of the infected cell.
Added by: Dr. Enrique Feoli
(2022-11-14 20:12:55)
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