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Porphyromonas gingivalis fuels colorectal cancer through CHI3L1-mediated iNKT cell-driven immune evasion.
- Source :
-
Gut microbes [Gut Microbes] 2024 Jan-Dec; Vol. 16 (1), pp. 2388801. Date of Electronic Publication: 2024 Aug 12. - Publication Year :
- 2024
-
Abstract
- The interaction between the gut microbiota and invariant Natural Killer T (iNKT) cells plays a pivotal role in colorectal cancer (CRC). The pathobiont Fusobacterium nucleatum influences the anti-tumor functions of CRC-infiltrating iNKT cells. However, the impact of other bacteria associated with CRC, like Porphyromonas gingivalis , on their activation status remains unexplored. In this study, we demonstrate that mucosa-associated P. gingivalis induces a protumour phenotype in iNKT cells, subsequently influencing the composition of mononuclear-phagocyte cells within the tumor microenvironment. Mechanistically, in vivo and in vitro experiments showed that P. gingivalis reduces the cytotoxic functions of iNKT cells, hampering the iNKT cell lytic machinery through increased expression of chitinase 3-like-1 protein (CHI3L1). Neutralization of CHI3L1 effectively restores iNKT cell cytotoxic functions suggesting a therapeutic potential to reactivate iNKT cell-mediated antitumour immunity. In conclusion, our data demonstrate how P. gingivalis accelerates CRC progression by inducing the upregulation of CHI3L1 in iNKT cells, thus impairing their cytotoxic functions and promoting host tumor immune evasion.
- Subjects :
- Humans
Animals
Mice
Tumor Microenvironment immunology
Immune Evasion
Tumor Escape
Gastrointestinal Microbiome immunology
Cell Line, Tumor
Bacteroidaceae Infections immunology
Bacteroidaceae Infections microbiology
Female
Mice, Inbred C57BL
Male
Colorectal Neoplasms immunology
Colorectal Neoplasms microbiology
Natural Killer T-Cells immunology
Porphyromonas gingivalis immunology
Chitinase-3-Like Protein 1 metabolism
Chitinase-3-Like Protein 1 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1949-0984
- Volume :
- 16
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Gut microbes
- Publication Type :
- Academic Journal
- Accession number :
- 39132842
- Full Text :
- https://doi.org/10.1080/19490976.2024.2388801