Activation of the unfolded protein response by Listeria monocytogenes

Pillich, Helena; Loose, Maria; Zimmer, Klaus–Peter; Chakraborty, Trinad

doi:10.1111/j.1462-5822.2012.01769.x

Cited by 101 publications

(113 citation statements)

References 61 publications

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“…Total RNA was extracted from RAW 264.7 cells (1 3 10 6 ) with RNeasy Plus (Qiagen, Hilden, Germany), and 1 mg total RNA was reverse transcribed into the first-strand cDNA with ImProm (Promega, Madison WI, USA) and oligo (dT) [12][13][14][15][16][17][18] primer, according to the manufacturer's instructions. Forward 59-CCGCAGCACTCAGACTATG-39 and reverse 59-GGGTCCAACTTGTCCAGAAT-39 pairs were used to amplify uXBP1 mRNA; forward 59-CTGAGTCCGCAGCAGGT-39and reverse 59-AAACATGACAGGGTCCAACTT-39 primers were used to amplify sXBP1 mRNA; forward: 59-TCCAAGAAAGGA-CGAACATTC-39 and reverse 59-TGAGGACATCTCCCACG-TCAA-39 primers were used to amplify IFN1-b; and forward 59-GTGTCCGTCGTGGATCTG-39 and reverse 59-TGCTTCAC-CACCTTCTTGA-39 primers were used to amplify GAPDH.…”

Section: Quantitative Real-time Pcrmentioning

confidence: 99%

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The integrated endoplasmic reticulum stress response in Leishmania amazonensis macrophage infection: the role of X‐box binding protein 1 transcription factor

et al. 2015

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Endoplasmic reticulum (ER) stress triggers the integrated ER-stress response (IERSR) that ensures cellular survival of ER stress and represents a primordial form of innate immunity. We investigated the role of IERSR during Leishmania amazonensis infection. Treatment of RAW 264.7 infected macrophages with the ER stress-inducing agent thapsigargin (TG; 1 mM) increased L. amazonensis infectivity in an IFN1-a receptor (IFNAR)-dependent manner. In Western blot assays, we showed that L. amazonensis activates the inositol-requiring enzyme (IRE1)/ X-box binding protein (XBP)-1-splicing arms of the IERSR in host cells. In chromatin immunoprecipitation (ChIP) assays, we showed an increased occupancy of enhancer and promoter sequences for the Ifnb gene by XBP1 in infected RAW 264.7 cells. Knocking down XBP1 expression by transducing RAW 264.7 cells with the short hairpin XBP1 lentiviral vector significantly reduced the parasite proliferation associated with impaired translocation of phosphorylated IFN regulatory transcription factor (IRF)-3 to the nucleus and a decrease in IFN1-b expression. Knocking down XBP1 expression also increased NO concentration, as determined by Griess reaction and reduced the expression of antioxidant genes, such as heme oxygenase (HO)-1, that protect parasites from oxidative stress. We conclude that L. amazonensis activation of XBP1 plays a critical role in infection by protecting the parasites from oxidative stress and increasing IFN1-b expression.-

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Section: Quantitative Real-time Pcrmentioning

confidence: 99%

“…Finally, XBP1 can be activated in some bacterial infections. For example, Listeria monocytogenes induces XBP1 splicing, which reduces the number of intracellular bacterial (17). Pseudomonas aeruginosa likewise triggers the IERSR and induces sXBP1 expression, to facilitate survival of the infected host cell (18).…”

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confidence: 99%

The integrated endoplasmic reticulum stress response in Leishmania amazonensis macrophage infection: the role of X‐box binding protein 1 transcription factor

et al. 2015

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“…Infection and comparison of WT and Atf6 −/− MEFs in vitro with Salmonella also yielded very similar observations. As our paper was being revised, an independent group reported proteolytic activation of ATF6 and ER stress after infection with Listeria monocytogenes (32). Cells infected with Listeria also mount autophagy as a defense mechanism (33).…”

mentioning

confidence: 91%

An IFN-γ–stimulated ATF6–C/EBP-β–signaling pathway critical for the expression of Death Associated Protein Kinase 1 and induction of autophagy

Gade¹,

Ramachandran²,

Maachani³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

112

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The IFN family of cytokines operates a frontline defense against pathogens and neoplastic cells in vivo by controlling the expression of several genes. The death-associated protein kinase 1 (DAPK1), an IFN-γ-induced enzyme, controls cell cycle, apoptosis, autophagy, and tumor metastasis, and its expression is frequently down-regulated in a number of human tumors. Although the biochemical action of DAPK1 is well understood, mechanisms that regulate its expression are unclear. Previously, we have shown that transcription factor C/EBP-β is required for the basal and IFN-γ-induced expression of DAPK1. Here, we show that ATF6, an ER stress-induced transcription factor, interacts with C/EBP-β in an IFN-stimulated manner and is obligatory for Dapk1 expression. IFN-stimulated proteolytic processing of ATF6 and ERK1/2-mediated phosphorylation of C/EBP-β are necessary for these interactions. More importantly, IFN-γ failed to activate autophagic response in cells lacking either ATF6 or C/EBP-β. Consistent with these observations, the Atf6 −/− mice were highly susceptible to lethal bacterial infections compared with the wild-type mice. These studies not only unravel an IFN signaling pathway that controls cell growth and antibacterial defense, but also expand the role of ATF6 beyond ER stress.

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“…This suggests that both stress and inflammatory genes are regulated via overlapping or even identical signaling hubs at all infection stages. Generally, stress responses during bacterial infections are initiated by diverse stimuli, most notably upon amino acid starvation in the cytosol or induction of stress at the endoplasmic reticulum (ER) (23,24). We observed that the transcriptional response to cytosolic, but not to vacuolar, WT Shigella infection resembles the amino acid starvation-induced stress response and involves regulation by the stress receptor GCN2 (data not shown).…”

Section: Resultsmentioning

confidence: 93%

Bacterial Internalization, Localization, and Effectors Shape the Epithelial Immune Response during Shigella flexneri Infection

et al. 2015

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Activation of the unfolded protein response by Listeria monocytogenes

Cited by 101 publications

References 61 publications

The integrated endoplasmic reticulum stress response in Leishmania amazonensis macrophage infection: the role of X‐box binding protein 1 transcription factor

The integrated endoplasmic reticulum stress response in Leishmania amazonensis macrophage infection: the role of X‐box binding protein 1 transcription factor

An IFN-γ–stimulated ATF6–C/EBP-β–signaling pathway critical for the expression of Death Associated Protein Kinase 1 and induction of autophagy

Bacterial Internalization, Localization, and Effectors Shape the Epithelial Immune Response during Shigella flexneri Infection

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