Phagocytosis of Microglia in the Central Nervous System Diseases

Abstract

Microglia, the resident macrophages of the central nervous system, rapidly activate in nearly all kinds of neurological diseases. These activated microglia become highly motile, secreting inflammatory cytokines, migrating to the lesion area, and phagocytosing cell debris or damaged neurons. During the past decades, the secretory property and chemotaxis of microglia have been well-studied, while relatively less attention has been paid to microglial phagocytosis. So far there is no obvious concordance with whether it is beneficial or detrimental in tissue repair. This review focuses on phagocytic phenotype of microglia in neurological diseases such as Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, traumatic brain injury, ischemic and other brain diseases. Microglial morphological characteristics, involved receptors and signaling pathways, distribution variation along with time and space changes, and environmental factors that affecting phagocytic function in each disease are reviewed. Moreover, a comparison of contributions between macrophages from peripheral circulation and the resident microglia to these pathogenic processes will also be discussed.

Role of microglia in fungal infections of the central nervous system

“…9 They can be found throughout the brain parenchyma, most commonly in the hippocampus and the retina. 10 The comparison between microglia and macrophage has facilitated our understanding of microglial physiology.…”

“…Myd88 is the key adaptor molecule in the TLR activation pathway against fungi and associates with the cytoplasmic part of TLR, 12 and subsequently recruits members of the IL-1b receptor associated kinase (IRAK) family, most importantly IRAK2 and IRAK4, which through TRAF6 downstream signaling leads to the translocation of NF-kB, and ultimately the release of inflammatory cytokines and interferon inducible genes. 9,12,36,49 Following Dectin-1 receptor activation by fungal cell wall antigens, Syk-CARD9 is the key adaptor molecule, 50 independent of Myd88 pathways, leading to NF-kB expression and Th17 responses. 51 TLR-2, 4, and 9, are associated with recognition of most fungal antigens, including the C. neoformans polysaccharide capsule, Candida albicans pseudohyphae, and Aspergillus spp.…”

Phagocytosis-dependent and independent mechanisms underlie the microglial cell damage caused by carbon nanotube agglomerates

“…Microglia are reported to migrate to the sites of cell death and aggregate to phagocytose cell debris (Nakajima and Kohsaka, 1993;Kreutzberg, 1996;Davalos et al, 2005;Hanisch and Kettenmann, 2007;Fu et al, 2014). Here, we determined that the number of microglial aggregates correlates well with microglial cell damage.…”

“…In pathological conditions of the CNS, microglia are acti-vated and trigger the endogenous defense/immune system (Nakajima and Kohsaka, 1993;Kreutzberg, 1996;Graeber and Streit, 2010;Kettenmann et al, 2011;Fu et al, 2014), including phagocytosis (Lai and Todd, 2006;Cartier et al, 2014). Microglia thereby determine the severity of the pathology, as macrophages do so outside the brain.…”

Protective effects of naringin against gp120-induced injury mediated by P2X7 receptors in BV2 microglial cells

“…However, it is commonly accepted that ADC is associated with the degree of immune suppression and the activation of macrophages and microglia cells (Harezlak et al, 2014). Various harmful substances can be produced by activated macrophages or microglia, which go on to damage other cells in the central nervous system (CNS) or induce apoptosis (Fu et al, 2014). Envelope glycoprotein gp120 (or gp120) is a glycoprotein found on the surface of the HIV envelope, and is essential for the virus' entry into cells as it plays a vital role in their attachment to specific cell-surface receptors (de Witte et al, 2007).…”