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Abstract

Studies have implicated that Adherent-invasive (AIEC) in the aetiology of Crohn’s Disease (CD), a chronic inflammatory bowel disease (IBD). CD-associated AIEC are characterised by an ability to adhere to and invade intestinal epithelial cells and replicate intracellularly in macrophages. This occurs as AIEC form vacuoles within phagolysosomes, preventing macrophage-mediated killing. However, little is known about the interaction of macrophage proteins with AIEC.

In this study, we used an infection model to identify macrophage proteins associated with AIEC intracellular replication. We identified the importance of proline-rich tyrosine kinase 2 (PYK2) in AIEC infection. PYK2 is widely expressed in epithelial cells and hematopoietic cells and plays essential roles in tumorigenesis and tumour progression. PYK2 is also overexpressed in patients with intestinal and colorectal cancer (CRC). CRC is one of the major long-term complications of IBD, especially in patients with long disease duration, a large extent of colitis, and uncontrolled inflammation. Moreover, PYK2 has been identified as an IBD risk loci via large scale genome-wide association studies.

Our models have demonstrated that the addition of PYK2 inhibitor PF-431396 during infection results in a significant decrease in intracellular replication of AIEC. This has been quantified using fluorescence immunostaining and imaging flow cytometry. These results suggest that PYK2 may play a role in intracellular bacteria survive and replication. Our future work aims to further understand the relationship between PYK2, AIEC and CD.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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/content/journal/acmi/10.1099/acmi.ac2020.po0267
2020-07-10
2021-10-18
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http://instance.metastore.ingenta.com/content/journal/acmi/10.1099/acmi.ac2020.po0267
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