Microglial Phagocytosis of Bacteria and Synapses
type: CreativeWork
description: Microglia, the resident brain macrophage, are essential for maintaining normal brain homeostasis through removal of pathogens - including bacteria and fungi - via phagocytosis. However, the mechanisms that regulate these phagocytic events are not clear. In this work, involvement of calreticulin, galectin-3, apolipoprotein E and β-amyloid in microglial phagocytosis of bacteria were studied. Microglia activated with bacterial endotoxin upregulated and released extracellular calreticulin and galectin-3 in culture, and both proteins could bind the surface of the gram-negative bacteria E. coli. Moreover, association of these proteins with the bacteria opsonised them for phagocytosis by microglia. This opsonisation was inhibitable by sugars, or by blocking microglial receptors MerTK or LRP1. LPS-activated microglia phagocytosed more E. coli than unactivated microglia, and this phagocytic induction was inhibited by an antibody against calreticulin, sugars, blocking MerTK or LRP1, or simply exchanging the cellular media. Thus, calreticulin and galectin-3 are bacterial opsonins, which may play an important role in immune responses to bacteria in the brain. Apolipoprotein E and β-amyloid – both of which are known to circulate extracellularly in the brain - also bound and opsonised E. coli for phagocytosis by microglia, and may further contribute to bacterial clearance in the brain. Extracellular nucleotides mediate a variety of microglial functions by binding receptors exposed by the microglia, including the phagocytic receptor P2Y6R and the chemotactic receptor P2Y12R. Both E. coli and inflammatory-activated microglia released extracellular agonist of P2Y6R, as did non-activated microglia, astrocytes and pheochromocytoma under specific experimental conditions. Exogenous UDP induced microglial phagocytosis of the bacteria in a time-sensitive manner, and this effect was inhibitable by blocking P2Y6R, suggesting that P2Y6R signalling regulates bacterial phagocytosis. Furthermor…
abstract: Microglia, the resident brain macrophage, are essential for maintaining normal brain homeostasis through removal of pathogens - including bacteria and fungi - via phagocytosis. However, the mechanisms that regulate these phagocytic events are not clear. In this work, involvement of calreticulin, galectin-3, apolipoprotein E and β-amyloid in microglial phagocytosis of bacteria were studied. Microglia activated with bacterial endotoxin upregulated and released extracellular calreticulin and galectin-3 in culture, and both proteins could bind the surface of the gram-negative bacteria E. coli. Moreover, association of these proteins with the bacteria opsonised them for phagocytosis by microglia. This opsonisation was inhibitable by sugars, or by blocking microglial receptors MerTK or LRP1. LPS-activated microglia phagocytosed more E. coli than unactivated microglia, and this phagocytic induction was inhibited by an antibody against calreticulin, sugars, blocking MerTK or LRP1, or simply exchanging the cellular media. Thus, calreticulin and galectin-3 are bacterial opsonins, which may play an important role in immune responses to bacteria in the brain. Apolipoprotein E and β-amyloid – both of which are known to circulate extracellularly in the brain - also bound and opsonised E. coli for phagocytosis by microglia, and may further contribute to bacterial clearance in the brain. Extracellular nucleotides mediate a variety of microglial functions by binding receptors exposed by the microglia, including the phagocytic receptor P2Y6R and the chemotactic receptor P2Y12R. Both E. coli and inflammatory-activated microglia released extracellular agonist of P2Y6R, as did non-activated microglia, astrocytes and pheochromocytoma under specific experimental conditions. Exogenous UDP induced microglial phagocytosis of the bacteria in a time-sensitive manner, and this effect was inhibitable by blocking P2Y6R, suggesting that P2Y6R signalling regulates bacterial phagocytosis. Furthermor…
author: Cockram, Thomas Oliver John
language: eng
keywords: Microglia, Phagocytosis, Bacteria, Synapse
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/1cb3a095-4b9f-4368-8324-8eb4d69599d4/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2020-05-19
date modified: 2026-07-22T22:24:25Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.53087