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A Novel Gastric Spheroid Co-culture Model Reveals Chemokine-Dependent Recruitment of Human Dendritic Cells to the Gastric Epithelium
- Source :
- Cellular and Molecular Gastroenterology and Hepatology, Vol 8, Iss 1, Pp 157-171.e3 (2019), Cellular and Molecular Gastroenterology and Hepatology
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Background & Aims: Gastric dendritic cells (DCs) control the adaptive response to infection with Helicobacter pylori, a major risk factor for peptic ulcer disease and gastric cancer. We hypothesize that DC interactions with the gastric epithelium position gastric DCs for uptake of luminal H pylori and promote DC responses to epithelial-derived mediators. The aim of this study was to determine whether the gastric epithelium actively recruits DCs using a novel co-culture model of human gastric epithelial spheroids and monocyte-derived DCs. Methods: Spheroid cultures of primary gastric epithelial cells were infected with H pylori by microinjection. Co-cultures were established by adding human monocyte-derived DCs to the spheroid cultures and were analyzed for DC recruitment and antigen uptake by confocal microscopy. Protein array, gene expression polymerase chain reaction array, and chemotaxis assays were used to identify epithelial-derived chemotactic factors that attract DCs. Data from the co-culture model were confirmed using human gastric tissue samples. Results: Human monocyte-derived DCs co-cultured with gastric spheroids spontaneously migrated to the gastric epithelium, established tight interactions with the epithelial cells, and phagocytosed luminally applied H pylori. DC recruitment was increased upon H pylori infection of the spheroids and involved the activity of multiple chemokines including CXCL1, CXCL16, CXCL17, and CCL20. Enhanced chemokine expression and DC recruitment to the gastric epithelium also was observed in H pylori–infected human gastric tissue samples. Conclusions: Our results indicate that the gastric epithelium actively recruits DCs for immunosurveillance and pathogen sampling through chemokine-dependent mechanisms, with increased recruitment upon active H pylori infection. Keywords: Stomach, Organoid, Mononuclear Phagocyte, In Vitro Model
- Subjects :
- Organoid
MoDC, monocyte-derived dendritic cell
RT-PCR, reverse-transcription polymerase chain reaction
0301 basic medicine
Chemokine
MNP, mononuclear phagocyte
Monocytes
0302 clinical medicine
In Vitro Model
ADC, dendritic cell
Cells, Cultured
Original Research
GFP, green fluorescent protein
Stomach
Gastroenterology
3. Good health
Organoids
Immunosurveillance
CXCL1
Editorial
medicine.anatomical_structure
030211 gastroenterology & hepatology
FITC, fluorescein isothiocyanate
Chemokines
TLR, Toll-like receptor
Biology
Helicobacter Infections
03 medical and health sciences
Spheroids, Cellular
medicine
Humans
lcsh:RC799-869
Mononuclear Phagocyte
CXCL16
CXCL17
Helicobacter pylori
Hepatology
Gene Expression Profiling
Epithelial Cells
Dendritic Cells
biology.organism_classification
Coculture Techniques
digestive system diseases
IL, interleukin
CagA, cytotoxin-associated antigen
CCL20
030104 developmental biology
Gene Expression Regulation
Gastric Mucosa
biology.protein
Cancer research
lcsh:Diseases of the digestive system. Gastroenterology
Subjects
Details
- ISSN :
- 2352345X
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Cellular and Molecular Gastroenterology and Hepatology
- Accession number :
- edsair.doi.dedup.....c9a7e4a980f84a71cc48f77e16e561af