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Functional role of galectin-9 in directing human innate immune reactions to Gram-negative bacteria and T cell apoptosis

Schlichtner, Stephanie, Helge Meyer, N., Yasinska, Inna M., Aliu, Nijas, Berger, Steffen M., Gibbs, Bernhard F, Fasler-Kan, Elizaveta, Sumbayev, Vadim V. (2021) Functional role of galectin-9 in directing human innate immune reactions to Gram-negative bacteria and T cell apoptosis. International Immunopharmacology, 100 . Article Number 108155. ISSN 1567-5769. (doi:10.1016/j.intimp.2021.108155) (KAR id:90466)

Abstract

Galectin-9 is a member of the galectin family of proteins, which were first identified to specifically bind to carbohydrates containing β-galactosides. Galectin-9 is conserved through evolution and recent evidence demonstrated its involvement in innate immune reactions to bacterial infections as well as the suppression of cytotoxic immune responses of T and natural killer cells. However, the molecular mechanisms underlying such differential immunological functions of galectin-9 remain largely unknown. In this work we confirmed that soluble galectin-9 derived from macrophages binds to Gram-negative bacteria by interacting with lipopolysaccharide (LPS), which forms their cell wall. This opsonisation effect most likely interferes with the mobility of bacteria leading to their phagocytosis by innate immune cells. Galectin-9-dependent opsonisation also promotes the innate immune reactions of macrophages to these bacteria and significantly enhances the production of proinflammatory cytokines – interleukin (IL) 6, IL-1β and tumour necrosis factor alpha (TNF-α). In contrast, galectin9 did not bind peptidoglycan (PGN), which forms the cell wall of Gram-positive bacteria. Moreover, galectin-9 associated with cellular surfaces (studied in primary human embryonic cells) was not involved in the interaction with bacteria or bacterial colonisation. However, galectin-9 expressed on the surface of primary human embryonic cells, as well as soluble forms of galectin-9, were able to target T lymphocytes and caused apoptosis in T cells expressing granzyme B. Furthermore, “opsonisation” of T cells by galectin-9 led to the translocation of phosphatidylserine onto the cell surface and subsequent phagocytosis by macrophages through Tim-3, the receptor, which recognises both galectin-9 and phosphatidylserine as ligands.

Item Type: Article
DOI/Identification number: 10.1016/j.intimp.2021.108155
Uncontrolled keywords: Galectin-9 Phagocytosis Anti-bacterial immune defence Embryonic development Anti-cancer immune evasion
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Vadim Sumbayev
Date Deposited: 20 Oct 2021 14:09 UTC
Last Modified: 06 Dec 2021 18:08 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/90466 (The current URI for this page, for reference purposes)

University of Kent Author Information

Gibbs, Bernhard F.

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CReDIT Contributor Roles:

Sumbayev, Vadim V..

Creator's ORCID: https://orcid.org/0000-0002-9404-5626
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