Figure 4.

Microglial phagocytosis in disease. In pathological conditions microglia is challenged and usually assumes a hypertrophic morphology. Challenged microglia phagocytose apoptotic and necrotic cells (A,B). In some inflammatory conditions, microglial phagocytosis can kill healthy neurons (C). Microglia also phagocytose axonal and myelin debris resulting from Wallerian degeneration of severed axons (D). (A) Surface-rendered fms-EGFP microglia (M; cyan) from the adult hippocampus phagocytosing three apoptotic/pycnotic cells (labeled with DAPI, white), in a mouse systemically challenged with bacterial lipopolysaccharides (5 mg/kg). (B) Electron microscopy microphotograph of embryonic (E20) microglia (N, microglial nucleus) from the rat cingulate cortex following maternal hypoxia (1 day) containing four engulfed dead cells. In the developing brain, hypoxia induces a whole range of death mechanisms, including apoptosis, pathological apoptosis, and necrosis (Blomgren et al., 2007). (C) Time-lapse imaging of microglia (red arrow) engulfing a live neuron (yellow arrow) in a co-culture challenged with the TLR2 agonist lipoteichoich acid (50 μg/ml). (D) Orthogonal projection of a confocal z-stack showing the engulfment of degenerated axons (labeled with tdTomato, red) by microglia (labeled with Iba1, green; nucleus labeled with DAPI, blue) in a co-culture model. Scale bars, 5 μm. Image (A) is reprinted with permission from Elsevier from Sierra et al. (2010). Image (B) is reprinted with permission from Elsevier from Li et al. (1998). Image (C) is reprinted with permission from Neher et al. (2011), Copyright 2011. The American Association of Immunologists., Inc. Image (D) is reprinted with permission from Hosmane et al. (2012).