Table 1.
Microglia act as sensors to multiple stimulations
| Stimulations | Biomarkers | Functions | References |
|---|---|---|---|
| Aging | IL-1β, IL-12, IL-23, TNF-α, iNOS, CD40, MHCI, MHCII and TREM2 | Lead to telomere shortening, DNA damage, and oxidative stress; Give rise to an increase in inflammatory states in the retina; impede spatial learning; lose inhibitory ligand-receptor correlations; accumulate misfolded proteins | Vijg and Campisi, 2008; Xu et al., 2008; Perry and Holmes, 2014; Rawji et al., 2016; Scheffold et al., 2016; Niraula et al., 2017; Wolf et al., 2017 |
| Stress | IL-1β, TNF-α, IL-6, CCL2, MHCII, TLR4 and CD14 | Aggravate behavioral abnormalities and neuroimmune responses | Frank et al., 2007; Wohleb et al., 2011; Prinz and Priller, 2014; Ramirez et al., 2015; Ramirez et al., 2016 |
| Injuries | TLR, RAGE, IL-1β and TNF-α; IL-4, IL-10 and TGF | Scavenge cell debris; long-term “innate immune memory” | Nimmerjahn et al., 2005; Haynes et al., 2006; Kono and Rock, 2008; Salminen et al., 2009; Perry et al., 2010 |
| Infections | MHCII, CD163, IL-1, TNF-α, S100β, IL-8, IL-6, CCL2/MCP-1 and CCL5/RANTES | Affect the apoptosis and survival pathway of microglia | Valle et al., 2004; Schwarcz et al., 2012; Chen et al., 2017 |
| Hypoxia | IL-1β, IL-6, TNF-α and TLR4 | Promote cell death and inflammation | Pineau and Lacroix, 2009; Tschopp and Schroder, 2010; Lim and Pack, 2014; McDonough et al., 2017; Cengiz et al., 2019 |
| ROS | TNF-α, IL-1β, iNOS, prostaglandin E2, and MCP-1 | Damage cellular molecules; change the structure of membrane | Naik and Dixit, 2011; Yang et al., 2011; D’Amico et al., 2013; Qin et al., 2013; Kierdorf and Prinz, 2017 |
| Microbiota | Slight increasing CSF1R and CD31 | Maintain homeostasis | Berer et al., 2011; Kamada et al., 2013; Miron et al., 2013; Braniste et al., 2014; Yano et al., 2015; Matcovitch-Natan et al., 2016 |
CCL2: CC-chemokine ligand 2; CCL5: CC-chemokine ligand 5; CSF1R: colony-stimulating factor-1 receptor; IL: interleukin; iNOS: inducible nitric oxide synthase; MCP-1: monocyte chemoattractant protein-1; MHC: major histocompatibility complex; RAGE: advanced glycation end products; RANTES: regulated upon activation, normal T cell expressed and secreted; ROS: reactive oxygen species; S100β: S100 calcium-binding protein β; TGF: transforming growth factor; TLR: Toll-like receptor; TNF-α: tumor necrosis factor-α; TREM2: triggering receptor expressed in the myeloid cell 2.