ArticleAutophagy2016
Activation of the EIF2AK4-EIF2A/eIF2α-ATF4 pathway triggers autophagy response to Crohn disease-associated adherent-invasive Escherichia coli infection.
Article in Autophagy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 70 citations in OpenAlex.
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- The role of amino acid signaling in pathogenesis of chronic kidney disease.Molecular and cellular biochemistry · 2026Review
- The assembly of a hybrid type IV secretion system by a Crohn's disease-associated Escherichia coli strain.Nature communications · 2025Article
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- EnterohemorrhagicPathogens (Basel, Switzerland) · 2025Article
- Autophagy and Bacterial infections.Autophagy reports · 2025Review
- ATG16L1 in myeloid cells limits colorectal tumor growth inAutophagy · 2024Article
- Insulin receptor orchestrates kidney antibacterial defenses.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Identification of autophagy receptors for the Crohn's disease-associated adherent-invasiveFrontiers in cellular and infection microbiology · 2024Article
- Exploring the Connections: Autophagy, Gut Microbiota, and Inflammatory Bowel Disease Pathogenesis.Journal of inflammation research · 2024Review
- Mitochondrial stress induces hepatic stellate cell activation in response to the ATF4/TRIB3 pathway stimulation.Journal of gastroenterology · 2023Article
- Crohn's disease: Why the ileum?World journal of gastroenterology · 2023Review
- AcrAB efflux pump impacts on the survival of adherent-invasive Escherichia coli strain LF82 inside macrophages.Scientific reports · 2023Article
- Article
- Article
- Reciprocal interactions between gut microbiota and autophagy.World journal of gastroenterology · 2021Review
- Targeting the integrated stress response in ophthalmology.Current eye research · 2021Review
- Colibactin-ProducingCancers · 2021Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The intestinal mucosa of Crohn disease (CD) patients is abnormally colonized by adherent-invasive E. coli (AIEC). Upon AIEC infection, autophagy is induced in host cells to restrain bacterial intracellular replication. The underlying mechanism, however, remains unknown. Here, we investigated the role of the EIF2AK4-EIF2A/eIF2α-ATF4 pathway in the autophagic response to AIEC infection. We showed that infection of human intestinal epithelial T84 cells with the AIEC reference strain LF82 activated the EIF2AK4-EIF2A-ATF4 pathway, as evidenced by increased phospho-EIF2AK4, phospho-EIF2A and ATF4 levels. EIF2AK4 depletion inhibited autophagy activation in response to LF82 infection, leading to increased LF82 intracellular replication and elevated pro-inflammatory cytokine production. Mechanistically, EIF2AK4 depletion suppressed the LF82-induced ATF4 binding to promoters of several autophagy genes including MAP1LC3B, BECN1, SQSTM1, ATG3 and ATG7, and this subsequently inhibited transcription of these genes. LF82 infection of wild-type (WT), but not eif2ak4(-/-), mice activated the EIF2AK4-EIF2A-ATF4 pathway, inducing autophagy gene transcription and autophagy response in enterocytes. Consequently, eif2ak4(-/-) mice exhibited increased intestinal colonization by LF82 bacteria and aggravated inflammation compared to WT mice. Activation of the EIF2AK4-EIF2A-ATF4 pathway was observed in ileal biopsies from patients with noninflamed CD, and this was suppressed in inflamed CD, suggesting that a defect in the activation of this pathway could be one of the mechanisms contributing to active disease. In conclusion, we show that activation of the EIF2AK4-EIF2A-ATF4 pathway upon AIEC infection serves as a host defense mechanism to induce functional autophagy to control AIEC intracellular replication.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.