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Macrophages Inability to Mediate Adherent-Invasive E. coli Replication is Linked to Autophagy in Crohn’s Disease Patients
- 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.
- Subjects :
- MESH: macrophages / pathology
autophagy
adherent-invasive e. coli
MESH: Crohn Disease / pathology
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
MESH: Crohn Disease / microbiology
[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology
IRGM
adherent-invasive E. coli
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
macrophages
ULK-1
MESH: Escherichia coli / pathogenicity
Crohn's disease
crohn’s disease
lcsh:Biology (General)
MESH: autophagy / genetics
MESH: Escherichia coli Infections / pathology
[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
irgm
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
ulk-1
lcsh:QH301-705.5
Subjects
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⟩