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Calreticulin and Galectin-3 Opsonise Bacteria for Phagocytosis by Microglia

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Cockram, Tom OJ 
Puigdellívol, Mar 
Brown, Guy C 


Opsonins are soluble, extracellular proteins, released by activated immune cells, and when bound to a target cell, can induce phagocytes to phagocytose the target cell. There are three known classes of opsonin: antibodies, complement factors and secreted pattern recognition receptors, but these have limited access to the brain. We identify here two novel opsonins of bacteria, calreticulin, and galectin-3 (both lectins that can bind lipopolysaccharide), which were released by microglia (brain-resident macrophages) when activated by bacterial lipopolysaccharide. Calreticulin and galectin-3 both bound to Escherichia coli, and when bound increased phagocytosis of these bacteria by microglia. Furthermore, lipopolysaccharide-induced microglial phagocytosis of E. coli bacteria was partially inhibited by: sugars, an anti-calreticulin antibody, a blocker of the calreticulin phagocytic receptor LRP1, a blocker of the galectin-3 phagocytic receptor MerTK, or simply removing factors released from the microglia, indicating this phagocytosis is dependent on extracellular calreticulin and galectin-3. Thus, calreticulin and galectin-3 are opsonins, released by activated microglia to promote clearance of bacteria. This innate immune response of microglia may help clear bacterial infections of the brain.



LRP1, MerTK, bacteria, calreticulin, galectin-3, microglia, opsonin, Animals, Brain, Calreticulin, Escherichia coli, Escherichia coli Infections, Galectin 3, Immunity, Innate, Mice, Microglia, Opsonin Proteins, Phagocytosis, Rats

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Frontiers in Immunology

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Frontiers Media SA


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Medical Research Council (MR/L010593/1)
Biotechnology and Biological Sciences Research Council (1645643)
This work was funded by the Biotechnology & Biological Sciences Research Council UK and the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 115976 (PHAGO consortium).