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Glucocorticoids Impair Phagocytosis and Inflammatory Response Against Crohn’s Disease-Associated Adherent-Invasive Escherichia coli
- Source :
- Frontiers in Immunology, Vol 9 (2018), Frontiers in Immunology
- Publication Year :
- 2018
- Publisher :
- Frontiers Media S.A., 2018.
-
Abstract
- Crohn’s disease (CD) is a chronic inflammatory bowel disorder characterized by deregulated inflammation triggered by environmental factors. Notably, adherent-invasive Escherichia coli (AIEC), a bacterium with the ability to survive within macrophages is believed to be one of such factors. Glucocorticoids are the first line treatment for CD and to date, it is unknown how they affect bactericidal and inflammatory properties of macrophages against AIEC. The aim of this study was to evaluate the impact of glucocorticoid treatment on AIEC infected macrophages. First, THP-1 cell-derived macrophages were infected with a CD2-a AIEC strain, in the presence or absence of the glucocorticoid dexamethasone (Dex) and mRNA microarray analysis was performed. Differentially expressed mRNAs were confirmed by TaqMan-qPCR. In addition, an amikacin protection assay was used to evaluate the phagocytic and bactericidal activity of Dex-treated macrophages infected with E. coli strains (CD2-a, HM605, NRG857c, and HB101). Finally, cytokine secretion and the inflammatory phenotype of macrophages were evaluated by ELISA and flow cytometry, respectively. The microarray analysis showed that CD2-a, Dex, and CD2-a + Dex-treated macrophages have differential inflammatory gene profiles. Also, canonical pathway analysis revealed decreased phagocytosis signaling by Dex and anti-inflammatory polarization on CD2-a + Dex macrophages. Moreover, amikacin protection assay showed reduced phagocytosis upon Dex treatment and TaqMan-qPCR confirmed Dex inhibition of three phagocytosis-associated genes. All bacteria strains induced TNF-α, IL-6, IL-23, CD40, and CD80, which was inhibited by Dex. Thus, our data demonstrate that glucocorticoids impair phagocytosis and induce anti-inflammatory polarization after AIEC infection, possibly contributing to the survival of AIEC in infected CD patients.
- Subjects :
- 0301 basic medicine
Crohn’s disease
lcsh:Immunologic diseases. Allergy
THP-1 Cells
Phagocytosis
Inflammatory response
Immunology
Nod2 Signaling Adaptor Protein
Real-Time Polymerase Chain Reaction
Bacterial Adhesion
Dexamethasone
Microbiology
03 medical and health sciences
Mice
0302 clinical medicine
Crohn Disease
Escherichia coli
polycyclic compounds
Medicine
Animals
Humans
Immunology and Allergy
INVASIVE ESCHERICHIA COLI
Escherichia coli Infections
Original Research
Inflammation
Mice, Knockout
Crohn's disease
glucocorticoids
business.industry
Tumor Necrosis Factor-alpha
phagocytosis
inflammatory response
medicine.disease
Microarray Analysis
macrophages
030104 developmental biology
adherent-invasive Escherichia coli
Cytokines
business
lcsh:RC581-607
hormones, hormone substitutes, and hormone antagonists
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....13b96d3dc9f4a9241e1c8b8f809b6bec