In:
The Journal of Immunology, The American Association of Immunologists, Vol. 202, No. 1_Supplement ( 2019-05-01), p. 51.6-51.6
Abstract:
H. pylori is a non-invasive bacterial pathogen that infects the lumen of the stomach and interacts with epithelial cells. In tissues from H. pylori infected and non-infected patients, DCs are found in close association with the gastric epithelium, which likely promotes DC uptake of luminal H. pylori. We hypothesized that DCs are recruited to the gastric epithelium in a chemokine-dependent manner. The aim of this study was to identify the epithelial chemokines that recruit DCs under steady state conditions and upon H. pylori infection. In chemotaxis assays, supernatants from human gastric organoids microinjected with H. pylori induced a 2-fold higher recruitment of monocyte-derived DCs compared to mock-infected organoids. Microscopic analysis of DC organoid-co-cultures similarly revealed DC recruitment to the epithelium of non-infected organoids and significantly increased recruitment upon H. pylori infection. DCs showed only low chemotactic activity towards H. pylori or bacterial supernatants, pointing to a role for epithelial rather than bacterial factors. DC migration towards the supernatants of both mock-infected and H. pylori-infected organoids was abrogated by pertussis toxin, indicating that recruitment was chemokine dependent. Using a chemokine array, we showed that organoid gastric organoids secreted increased amounts CXCL1, 5, 8 and CCL20 upon H. pylori infection, while CXCL16 and 17 remained constant. Chemotaxis assays confirmed that human DCs show chemotactic responses to CXCL1, 5, 8, 16, 17 and CCL20. In summary, our study indicates that human gastric epithelial cells actively recruit DCs to the mucosal interface by secreting chemokines, with increased recruitment induced upon H. pylori infection.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.202.Supp.51.6
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2019
detail.hit.zdb_id:
1475085-5
detail.hit.zdb_id:
3056-9
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