The multiple roles of the innate immune system in the regulation of apoptosis and inflammation in the brain.
Central nervous system (CNS) tissues contain cells (i.e. glia and neurons) that have innate immune functions. These cells express a range of receptors that are capable of detecting and clearing apoptotic cells and regulating inflammatory responses. Phagocytosis of apoptotic cells is a nonphlogistic (i.e. noninflammatory) process that provides immune regulation through anti-inflammatory cytokines andregulatory T cells. Neurons and glia express cellular death signals, including CD95Fas/CD95L, FasL, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and tumor necrosis factor receptor 1 (TNFR), through which they can trigger apoptosis in T cells and other infiltrating cells. Microglia, astrocytes, ependymal cells, and neurons express defense collagens and scavenger and phagocytic receptors that recognize apoptotic cells displaying apoptotic cell-associated molecular patterns, which serve as markers of "altered self." Glia also express pentraxins and complement proteins (C1q, C3b, and iC3b) that opsonize apoptotic cells, making them targets for the phagocytic receptors CR3 and CR4. Immunoregulatory molecules such as the complement regulator CD46 are lost from apoptotic cells and stimulate phagocytosis, whereas the expression of CD47 and CD200 is upregulated during apoptosis; this inhibits proinflammatory microglial cytokine expression, thereby reducing the severity of inflammation. This review outlines the cellular pathways used for the detection and phagocytosis of apoptotic cells in vitro and in experimental models of CNS inflammation.
Griffiths
Mark R
MR
Departments of Medical Biochemistry, University of Cardiff Medical School, Cardiff, United Kingdom.
Gasque
Philippe
P
Neal
James W
JW
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology*; D009457:Neuroglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010587:Phagocytosis / Q000276:immunology