On the TRAIL of lymphocyte death in measles

Abstract

Measles virus (MV) infection is still a major cause of childhood mortality in developing countries. MV causes severe immunosuppression, which allows secondary infection of the host and it is these secondary infections that can cause death. Several mechanisms for MV-induced immunosuppression have been proposed, including inhibition of interleukin (IL)-12 production by monocytes/macrophages and dendritic cells by crosslinking of the MV cellular receptor, CD46; the production of soluble inhibitory factors; negative signalling to T cells by antigen-presenting cells; retardation of lymphocytes in specific stages of the cell cycle; and lymphocyte apoptosis. A recent paper by Vidalain et al.1xMeasles virus induces functional TRAIL production by human dendritic cells. Vidalain, P-O. et al. J. Virol. 2000; 74: 556–559Crossref | PubMedSee all References1, further pursuing the mechanisms of lymphocyte apoptosis, has shown that tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) expression is upregulated in human dendritic cells upon MV infection, and this mediates apoptosis of cells that interact with these dendritic cells. Surprisingly, TRAIL is not readily detectable on the surface of MV-infected dendritic cells, but appears to remain internalized after MV infection. However, apoptosis of MDA-231 cells induced by MV-infected dendritic cells and monocytes appears to be mediated by TRAIL, as a soluble TRAIL-receptor-2 construct inhibits the apoptotic-inducing activity of the accessory cells. Previously, TRAIL was thought to be important in apoptotic killing of transformed cells but the evidence here, and other data coming from HIV research, suggests that it could also be involved in lymphocyte apoptosis, especially after certain infections.