The role of Siglecs in the interaction between colon cancer-associated Fusobacterium nucleatum strains and the host immune system

Ali, Manasik Gumah Adam (2025) The role of Siglecs in the interaction between colon cancer-associated Fusobacterium nucleatum strains and the host immune system. Doctoral thesis, University of East Anglia.

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Abstract

Colorectal cancer (CRC) is among the three most common types of cancer worldwide. Fusobacterium nucleatum subsp. is one of the primary bacterial species involved in the initiation, progression, and metastasis of CRC. F. nucleatum subsp. animalis, the dominant subspecies in CRC tissues, has been previously shown to interact with Siglec-7, a member of the sialic acid-binding immunoglobulin-like lectin (Siglec) superfamily. This interaction also occurred with F. nucleatum-derived outer membrane vesicles (OMVs) and lipopolysaccharide (LPS). However, the mechanisms underlying F. nucleatum binding to Siglec-7 and how this interaction influences immune response remain unclear.

Here, we purified Siglec-7-Fc from Chinese Hamster Ovary (CHO) mammalian cells and successfully expressed recombinant Siglec-7WT and its mutant, Siglec-7R124A, in Escherichia coli and confirmed that the proteins are functional. We showed that OMVs and LPS purified from F. nucleatum ATCC 10953, ATCC 25586 and ATCC 51191 strains bound to Siglec-7 via the canonical Arginine (Arg124). The interaction of F. nucleatum-derived OMVs and LPS with Siglec-7 induced a pro-inflammatory phenotype in monocyte-derived dendritic cells, an M2 phenotype in monocyte-derived macrophages, and promoted cytokine production and T cell maturation into T helper Th1 and Th2 subsets in a Siglec-7-dependent manner. Furthermore, we demonstrated that F. nucleatum subsp., OMVs and LPS activate the TLR4/NF-κB signalling pathway in vitro.

Using a human colonic organoid monolayer model, we showed that F. nucleatum subsp., OMVs and LPS induced a strong cytokine response while intestinal barrier integrity remained largely unchanged.

Together, these data provided novel insights into the capacity of F. nucleatum strains to influence host response.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Chris White
Date Deposited:	01 Dec 2025 14:38
Last Modified:	01 Dec 2025 14:38
URI:	https://ueaeprints.uea.ac.uk/id/eprint/101169
DOI:

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