Identification of autophagy receptors for the Crohn’s disease-associated adherent-invasive Escherichia coli
IntroductionCrohn’s disease (CD) is a chronic inflammatory bowel disease, of which the etiology involves genetic, environmental and microbial factors. Adherent-invasive Escherichia coli (AIEC) and polymorphisms in autophagy-related genes have been implicated in CD etiology. Autophagy is a key proces...
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1268243/full |
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| author | Alison Da Silva Guillaume Dalmasso Anaïs Larabi My Hanh Thi Hoang My Hanh Thi Hoang Elisabeth Billard Nicolas Barnich Hang Thi Thu Nguyen |
| author_facet | Alison Da Silva Guillaume Dalmasso Anaïs Larabi My Hanh Thi Hoang My Hanh Thi Hoang Elisabeth Billard Nicolas Barnich Hang Thi Thu Nguyen |
| author_sort | Alison Da Silva |
| collection | DOAJ |
| description | IntroductionCrohn’s disease (CD) is a chronic inflammatory bowel disease, of which the etiology involves genetic, environmental and microbial factors. Adherent-invasive Escherichia coli (AIEC) and polymorphisms in autophagy-related genes have been implicated in CD etiology. Autophagy is a key process for the maintenance of cellular homeostasis, which allows the degradation of damaged cytoplasmic components and pathogens via lysosome. We have shown that a functional autophagy is necessary for AIEC clearance. Here, we aimed at identifying the autophagy receptor(s) responsible to target AIEC to autophagy for degradation.MethodsThe levels of autophagy receptors p62, NDP52, NBR1, TAX1BP1 and Optineurin were knocked down in human intestinal epithelial cells T84 using siRNAs. The NDP52 knock-out (KO) and p62 KO HeLa cells, as well as NDP52 KO HeLa cells expressing the wild-type NDP52 or the mutated NDP52Val248Ala protein were used.Results and discussionWe showed that, among the tested autophagy receptors (p62, NDP52, NBR1, TAX1BP1 and Optineurin), diminished expression of p62 or NDP52 increased the number of the clinical AIEC LF82 strain inside epithelial cells. This was associated with increased pro-inflammatory cytokine production. Moreover, p62 or NDP52 directly colocalized with AIEC LF82 and LC3, an autophagy marker. As the NDP52Val248Ala polymorphism has been associated with increased CD susceptibility, we investigated its impact on AIEC control. However, in HeLa cell and under our experimental condition, no effect of this polymorphism neither on AIEC LF82 intracellular number nor on pro-inflammatory cytokine production was observed. Together, our results suggest that p62 and NDP52 act as autophagy receptors for AIEC recognition, controlling AIEC intracellular replication and inflammation. |
| first_indexed | 2024-04-24T17:36:49Z |
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| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-24T17:36:49Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-03fdb2e074c042aebb0411b73a6b72b42024-03-28T04:32:50ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882024-03-011410.3389/fcimb.2024.12682431268243Identification of autophagy receptors for the Crohn’s disease-associated adherent-invasive Escherichia coliAlison Da Silva0Guillaume Dalmasso1Anaïs Larabi2My Hanh Thi Hoang3My Hanh Thi Hoang4Elisabeth Billard5Nicolas Barnich6Hang Thi Thu Nguyen7M2iSH (Microbes, Intestine, Inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRAE USC 1382, CNRH, Clermont-Ferrand, FranceM2iSH (Microbes, Intestine, Inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRAE USC 1382, CNRH, Clermont-Ferrand, FranceM2iSH (Microbes, Intestine, Inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRAE USC 1382, CNRH, Clermont-Ferrand, FranceM2iSH (Microbes, Intestine, Inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRAE USC 1382, CNRH, Clermont-Ferrand, FranceDepartment of Cell Biology, Faculty of Biology, University of Science, Vietnam National University, Hanoi, VietnamM2iSH (Microbes, Intestine, Inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRAE USC 1382, CNRH, Clermont-Ferrand, FranceM2iSH (Microbes, Intestine, Inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRAE USC 1382, CNRH, Clermont-Ferrand, FranceM2iSH (Microbes, Intestine, Inflammation and Susceptibility of the Host), UMR 1071 Inserm, Université Clermont Auvergne, INRAE USC 1382, CNRH, Clermont-Ferrand, FranceIntroductionCrohn’s disease (CD) is a chronic inflammatory bowel disease, of which the etiology involves genetic, environmental and microbial factors. Adherent-invasive Escherichia coli (AIEC) and polymorphisms in autophagy-related genes have been implicated in CD etiology. Autophagy is a key process for the maintenance of cellular homeostasis, which allows the degradation of damaged cytoplasmic components and pathogens via lysosome. We have shown that a functional autophagy is necessary for AIEC clearance. Here, we aimed at identifying the autophagy receptor(s) responsible to target AIEC to autophagy for degradation.MethodsThe levels of autophagy receptors p62, NDP52, NBR1, TAX1BP1 and Optineurin were knocked down in human intestinal epithelial cells T84 using siRNAs. The NDP52 knock-out (KO) and p62 KO HeLa cells, as well as NDP52 KO HeLa cells expressing the wild-type NDP52 or the mutated NDP52Val248Ala protein were used.Results and discussionWe showed that, among the tested autophagy receptors (p62, NDP52, NBR1, TAX1BP1 and Optineurin), diminished expression of p62 or NDP52 increased the number of the clinical AIEC LF82 strain inside epithelial cells. This was associated with increased pro-inflammatory cytokine production. Moreover, p62 or NDP52 directly colocalized with AIEC LF82 and LC3, an autophagy marker. As the NDP52Val248Ala polymorphism has been associated with increased CD susceptibility, we investigated its impact on AIEC control. However, in HeLa cell and under our experimental condition, no effect of this polymorphism neither on AIEC LF82 intracellular number nor on pro-inflammatory cytokine production was observed. Together, our results suggest that p62 and NDP52 act as autophagy receptors for AIEC recognition, controlling AIEC intracellular replication and inflammation.https://www.frontiersin.org/articles/10.3389/fcimb.2024.1268243/fulladherent-invasive E. coli (AIEC)autophagyCrohn’s diseasep62NDP52 |
| spellingShingle | Alison Da Silva Guillaume Dalmasso Anaïs Larabi My Hanh Thi Hoang My Hanh Thi Hoang Elisabeth Billard Nicolas Barnich Hang Thi Thu Nguyen Identification of autophagy receptors for the Crohn’s disease-associated adherent-invasive Escherichia coli Frontiers in Cellular and Infection Microbiology adherent-invasive E. coli (AIEC) autophagy Crohn’s disease p62 NDP52 |
| title | Identification of autophagy receptors for the Crohn’s disease-associated adherent-invasive Escherichia coli |
| title_full | Identification of autophagy receptors for the Crohn’s disease-associated adherent-invasive Escherichia coli |
| title_fullStr | Identification of autophagy receptors for the Crohn’s disease-associated adherent-invasive Escherichia coli |
| title_full_unstemmed | Identification of autophagy receptors for the Crohn’s disease-associated adherent-invasive Escherichia coli |
| title_short | Identification of autophagy receptors for the Crohn’s disease-associated adherent-invasive Escherichia coli |
| title_sort | identification of autophagy receptors for the crohn s disease associated adherent invasive escherichia coli |
| topic | adherent-invasive E. coli (AIEC) autophagy Crohn’s disease p62 NDP52 |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1268243/full |
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