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Macrophages Inability to Mediate Adherent-Invasive E. coli Replication is Linked to Autophagy in Crohn’s Disease Patients

Authors :
Buisson, Anthony
Douadi, Clara
Ouchchane, Lemlhi
Goutte, Marion
Hugot, Jean-Pierre
Dubois, Anaëlle
Minet-Quinard, Régine
Bouvier, Damien
Bommelaer, Gilles
Vazeille, Emilie
Barnich, Nicolas
Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH)
Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de la Recherche Agronomique (INRA)
Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand]
CHU Estaing [Clermont-Ferrand]
CHU Clermont-Ferrand-CHU Clermont-Ferrand
Institut Pascal (IP)
SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149))
Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
CHU Clermont-Ferrand
Broad medical program-Crohn's Colitis Foundation of America
'Societe Nationale Francaise de Gastroenterologie' (SNFGE)
Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)
OUERTANI, jeannette
Source :
Cells, Vol 8, Iss 11, p 1394 (2019), Cells, Cells, MDPI, 2019, 8 (11), pp.1-17. ⟨10.3390/cells8111394⟩, Cells, 2019, 8 (11), pp.1-17. ⟨10.3390/cells8111394⟩
Publication Year :
2019
Publisher :
MDPI AG, 2019.

Abstract

The macrophages from Crohn’s Disease (CD) patients are defective to control the replication of CD-associated adherent-invasive E. coli (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 (p = 0.0019). AIEC bacteria survival increased in patients with CD-associated polymorphism IRGM (p = 0.05) and reduced in those with CD-associated polymorphisms XBP-1 (p = 0.026) and ULK-1 (p = 0.033). AIEC infection led to an increase of pro-inflammatory cytokines IL-1β (p < 0.0001) and TNF-α (p < 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 (p = 0.0056) and correlated with AIEC survival (p = 0.0013). Moreover, the expression of ULK-1 phosphorylation on Serine 757 decreased following to AIEC infection (p < 0.0001). Short-term silencing of ULK-1 and IRGM genes restricted and promote, respectively, AIEC survival within MDM (p = 0.0018 and p = 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.

Details

Language :
English
ISSN :
20734409
Volume :
8
Issue :
11
Database :
OpenAIRE
Journal :
Cells
Accession number :
edsair.dedup.wf.001..1bdde49ddc1f1bfda5cfee945d44cab0
Full Text :
https://doi.org/10.3390/cells8111394⟩