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Open AccessArticle

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

1
University of Clermont Auvergne/Inserm U1071, USC-INRA 2018, Microbes, Intestine, Inflammation and Host susceptibility (M2iSH), 63001 Clermont-Ferrand, France
2
University of Clermont Auvergne, Inserm, 3iHP, University Hospital Clermont-Ferrand, Hepato-Gastro Enterology Department, 63100 Clermont-Ferrand, France
3
University of Clermont Auvergne, University Hospital Clermont-Ferrand, CNRS, SIGMA Clermont, Pascal Institute, 63000 Clermont-Ferrand, France
4
UMR843, Inserm, Assistance Publique Hôpitaux de Paris et Université (AP-HP), Paris Diderot, 75013 Paris, France
5
Biochemistry laboratory, University Hospital Estaing, Clermont-Ferrand 63100, France
*
Authors to whom correspondence should be addressed.
A.B. and C.D. share first authorship.
Cells 2019, 8(11), 1394; https://doi.org/10.3390/cells8111394
Received: 3 September 2019 / Revised: 24 October 2019 / Accepted: 30 October 2019 / Published: 5 November 2019
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.
Keywords: Crohn’s disease; macrophages; adherent-invasive E. coli; IRGM; ULK-1; autophagy Crohn’s disease; macrophages; adherent-invasive E. coli; IRGM; ULK-1; autophagy
MDPI and ACS Style

Buisson, A.; Douadi, C.; Ouchchane, L.; Goutte, M.; Hugot, J.-P.; Dubois, A.; Minet-Quinard, R.; Bouvier, D.; Bommelaer, G.; Vazeille, E.; Barnich, N. Macrophages Inability to Mediate Adherent-Invasive E. coli Replication is Linked to Autophagy in Crohn’s Disease Patients. Cells 2019, 8, 1394.

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