Novel inhibitory effect of galectin-3 on the respiratory burst induced by Staphylococcus aureus in human neutrophils

Vignesh Venkatakrishnan, Jonas Elmwall, Trisha Lahiri, Martina Sundqvist, Linda Bergqvist, Hakon Leffler, Ulf J Nilsson, Amanda Welin, Johan Bylund, Anna Karlsson-Bengtsson

Research output: Contribution to journalArticlepeer-review

Abstract

Among the responders to microbial invasion, neutrophils represent the earliest and perhaps the most important immune cells that contribute to host defense with the primary role to kill invading microbes using a plethora of stored anti-microbial molecules. One such process is the production of reactive oxygen species (ROS) by the neutrophil enzyme complex NADPH-oxidase, which can be assembled and active either extracellularly or intracellularly in phagosomes (during phagocytosis) and/or granules (in absence of phagocytosis). One soluble factor modulating the interplay between immune cells and microbes is galectin-3 (gal-3), a carbohydrate-binding protein that regulates a wide variety of neutrophil functions. Gal-3 has been shown to potentiate neutrophil interaction with bacteria, including Staphylococcus aureus, and is also a potent activator of the neutrophil respiratory burst, inducing large amounts of granule-localized ROS in primed cells. Herein, the role of gal-3 in regulating S. aureus phagocytosis and S. aureus-induced intracellular ROS was analyzed by imaging flow cytometry and luminol-based chemiluminescence, respectively. While gal-3 did not interfere with S. aureus phagocytosis per se, it potently inhibited phagocytosis-induced intracellular ROS production. Using the gal-3 inhibitor GB0139 (TD139) and gal-3C we found that the gal-3-induced inhibitory effect on ROS production was dependent on the carbohydrate recognition domain of the lectin. In summary, this is the first report of an inhibitory role of gal-3 in regulating phagocytosis-induced ROS production.

Original languageEnglish
Pages (from-to)503-511
Number of pages9
JournalGlycobiology
Volume33
Issue number6
Early online date2023 Apr 18
DOIs
Publication statusPublished - 2023 Jun 21

Subject classification (UKÄ)

  • Immunology in the medical area

Free keywords

  • Staphylococcus aureus
  • galectin-3
  • neutrophils
  • phagocytosis
  • reactive oxygen species

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