Macrophages Inability to Mediate Adherent-Invasive <i>E. coli</i> Replication is Linked to Autophagy in Crohn’s Disease Patients
The macrophages from Crohn’s Disease (CD) patients are defective to control the replication of CD-associated adherent-invasive <i>E. coli</i> (AIEC). We aimed to identify the host factors associated with AIEC replication focusing on polymorphisms related to autophagy. Periphera...
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MDPI AG
2019-11-01
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| Online Access: | https://www.mdpi.com/2073-4409/8/11/1394 |
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| author | Anthony Buisson Clara Douadi Lemlih Ouchchane Marion Goutte Jean-Pierre Hugot Anaëlle Dubois Régine Minet-Quinard Damien Bouvier Gilles Bommelaer Emilie Vazeille Nicolas Barnich |
| author_facet | Anthony Buisson Clara Douadi Lemlih Ouchchane Marion Goutte Jean-Pierre Hugot Anaëlle Dubois Régine Minet-Quinard Damien Bouvier Gilles Bommelaer Emilie Vazeille Nicolas Barnich |
| author_sort | Anthony Buisson |
| collection | DOAJ |
| description | The macrophages from Crohn’s Disease (CD) patients are defective to control the replication of CD-associated adherent-invasive <i>E. coli</i> (AIEC). We aimed to identify the host factors associated with AIEC replication focusing on polymorphisms related to autophagy. Peripheral blood monocyte-derived macrophages (MDM), obtained from 95 CD patient, 30 ulcerative colitis (UC) patients and 15 healthy subjects, were genotyped for several CD-associated polymorphisms. AIEC bacteria survival increased within MDM from CD patients compared to UC (<i>p</i> = 0.0019). AIEC bacteria survival increased in patients with CD-associated polymorphism <i>IRGM</i> (<i>p</i> = 0.05) and reduced in those with CD-associated polymorphisms <i>XBP-1</i> (<i>p</i> = 0.026) and <i>ULK-1</i> (<i>p</i> = 0.033). AIEC infection led to an increase of pro-inflammatory cytokines IL-1β (<i>p</i> < 0.0001) and TNF-α (<i>p</i> < 0.0001) in CD macrophages. ULK-1 expression increased in AIEC-infected MDM from CD patients compared to MDM from UC patients or healthy subjects (<i>p</i> = 0.0056) and correlated with AIEC survival (<i>p</i> = 0.0013). Moreover, the expression of ULK-1 phosphorylation on Serine 757 decreased following to AIEC infection (<i>p</i> < 0.0001). Short-term silencing of ULK-1 and IRGM genes restricted and promote, respectively, AIEC survival within MDM (<i>p</i> = 0.0018 and <i>p</i> = 0.0291). In conclusion, the macrophage defect to mediate AIEC clearance in CD patients is linked to polymorphisms related to autophagy such as IRGM and ULK-1. |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T08:20:49Z |
| publishDate | 2019-11-01 |
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| spelling | doaj.art-78b1cf683ebb4116b8a62ae0b9007f072023-09-02T18:28:34ZengMDPI AGCells2073-44092019-11-01811139410.3390/cells8111394cells8111394Macrophages Inability to Mediate Adherent-Invasive <i>E. coli</i> Replication is Linked to Autophagy in Crohn’s Disease PatientsAnthony Buisson0Clara Douadi1Lemlih Ouchchane2Marion Goutte3Jean-Pierre Hugot4Anaëlle Dubois5Régine Minet-Quinard6Damien Bouvier7Gilles Bommelaer8Emilie Vazeille9Nicolas Barnich10University of Clermont Auvergne/Inserm U1071, USC-INRA 2018, Microbes, Intestine, Inflammation and Host susceptibility (M2iSH), 63001 Clermont-Ferrand, FranceUniversity of Clermont Auvergne/Inserm U1071, USC-INRA 2018, Microbes, Intestine, Inflammation and Host susceptibility (M2iSH), 63001 Clermont-Ferrand, FranceUniversity of Clermont Auvergne, University Hospital Clermont-Ferrand, CNRS, SIGMA Clermont, Pascal Institute, 63000 Clermont-Ferrand, FranceUniversity of Clermont Auvergne/Inserm U1071, USC-INRA 2018, Microbes, Intestine, Inflammation and Host susceptibility (M2iSH), 63001 Clermont-Ferrand, FranceUMR843, Inserm, Assistance Publique Hôpitaux de Paris et Université (AP-HP), Paris Diderot, 75013 Paris, FranceUniversity of Clermont Auvergne/Inserm U1071, USC-INRA 2018, Microbes, Intestine, Inflammation and Host susceptibility (M2iSH), 63001 Clermont-Ferrand, FranceBiochemistry laboratory, University Hospital Estaing, Clermont-Ferrand 63100, FranceBiochemistry laboratory, University Hospital Estaing, Clermont-Ferrand 63100, FranceUniversity of Clermont Auvergne, Inserm, 3iHP, University Hospital Clermont-Ferrand, Hepato-Gastro Enterology Department, 63100 Clermont-Ferrand, FranceUniversity of Clermont Auvergne/Inserm U1071, USC-INRA 2018, Microbes, Intestine, Inflammation and Host susceptibility (M2iSH), 63001 Clermont-Ferrand, FranceUniversity of Clermont Auvergne/Inserm U1071, USC-INRA 2018, Microbes, Intestine, Inflammation and Host susceptibility (M2iSH), 63001 Clermont-Ferrand, FranceThe macrophages from Crohn’s Disease (CD) patients are defective to control the replication of CD-associated adherent-invasive <i>E. coli</i> (AIEC). We aimed to identify the host factors associated with AIEC replication focusing on polymorphisms related to autophagy. Peripheral blood monocyte-derived macrophages (MDM), obtained from 95 CD patient, 30 ulcerative colitis (UC) patients and 15 healthy subjects, were genotyped for several CD-associated polymorphisms. AIEC bacteria survival increased within MDM from CD patients compared to UC (<i>p</i> = 0.0019). AIEC bacteria survival increased in patients with CD-associated polymorphism <i>IRGM</i> (<i>p</i> = 0.05) and reduced in those with CD-associated polymorphisms <i>XBP-1</i> (<i>p</i> = 0.026) and <i>ULK-1</i> (<i>p</i> = 0.033). AIEC infection led to an increase of pro-inflammatory cytokines IL-1β (<i>p</i> < 0.0001) and TNF-α (<i>p</i> < 0.0001) in CD macrophages. ULK-1 expression increased in AIEC-infected MDM from CD patients compared to MDM from UC patients or healthy subjects (<i>p</i> = 0.0056) and correlated with AIEC survival (<i>p</i> = 0.0013). Moreover, the expression of ULK-1 phosphorylation on Serine 757 decreased following to AIEC infection (<i>p</i> < 0.0001). Short-term silencing of ULK-1 and IRGM genes restricted and promote, respectively, AIEC survival within MDM (<i>p</i> = 0.0018 and <i>p</i> = 0.0291). In conclusion, the macrophage defect to mediate AIEC clearance in CD patients is linked to polymorphisms related to autophagy such as IRGM and ULK-1.https://www.mdpi.com/2073-4409/8/11/1394crohn’s diseasemacrophagesadherent-invasive <i>e. coli</i><i>irgm</i><i>ulk-1</i>autophagy |
| spellingShingle | Anthony Buisson Clara Douadi Lemlih Ouchchane Marion Goutte Jean-Pierre Hugot Anaëlle Dubois Régine Minet-Quinard Damien Bouvier Gilles Bommelaer Emilie Vazeille Nicolas Barnich Macrophages Inability to Mediate Adherent-Invasive <i>E. coli</i> Replication is Linked to Autophagy in Crohn’s Disease Patients Cells crohn’s disease macrophages adherent-invasive <i>e. coli</i> <i>irgm</i> <i>ulk-1</i> autophagy |
| title | Macrophages Inability to Mediate Adherent-Invasive <i>E. coli</i> Replication is Linked to Autophagy in Crohn’s Disease Patients |
| title_full | Macrophages Inability to Mediate Adherent-Invasive <i>E. coli</i> Replication is Linked to Autophagy in Crohn’s Disease Patients |
| title_fullStr | Macrophages Inability to Mediate Adherent-Invasive <i>E. coli</i> Replication is Linked to Autophagy in Crohn’s Disease Patients |
| title_full_unstemmed | Macrophages Inability to Mediate Adherent-Invasive <i>E. coli</i> Replication is Linked to Autophagy in Crohn’s Disease Patients |
| title_short | Macrophages Inability to Mediate Adherent-Invasive <i>E. coli</i> Replication is Linked to Autophagy in Crohn’s Disease Patients |
| title_sort | macrophages inability to mediate adherent invasive i e coli i replication is linked to autophagy in crohn s disease patients |
| topic | crohn’s disease macrophages adherent-invasive <i>e. coli</i> <i>irgm</i> <i>ulk-1</i> autophagy |
| url | https://www.mdpi.com/2073-4409/8/11/1394 |
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