title: Contribution of dendritic cells to measles virus induced immunosuppression.
abstract: Measles virus (MV) remains an important pathogen in children worldwide. The morbidity and mortality of MV is associated with severe immune suppression. Dendritic cells (DCs) were identified as initial target cells in vivo, and DCs were efficiently infected by MV in vitro. MV infection of DCs likely contributes to functional deficiency in these cells; therefore playing a role in MV-induced immunosuppression. DCs appeared to mature phenotypically; however, the ability of infected cells to stimulate T cells was compromised. Phenotypic maturation of infected immature DCs was partially controlled by IFN production; however, infected DCs also maintained markers of an immature phenotype such as the continued uptake of antigen and lack of expression of chemokine receptor CCR7. Furthermore, mature DCs did not appear to maintain phenotypic maturation following infection demonstrated by decreased MHC and co-stimulatory molecule expression. Several mechanisms of MV-induced DC dysfunction have been suggested, each likely contributing to the immunosuppressive effect of MV-infected DCs. Infected DCs responded aberrantly to secondary maturation stimuli such as CD40L or TLR4 stimulation. MV infection resulted in apoptosis in DC/T-cell cocultures, which may contribute to a reduced T-cell response. Additionally, the immunological synapse between infected DCs and T cells was compromised resulting in reduced T-cell interaction times and activation signaling. The mechanisms of MV contribution to DC dysfunction appear multifaceted and central to MV-induced immunosuppression.
authors.affiliation: Centers for Disease Control and Prevention, Measles, Mumps, Rubella and Herpesvirus Laboratory Branch, Atlanta, GA 30333, USA.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Coughlin
authors.forename: William J
authors.initials: WJ
authors.lastname: Bellini
authors.forename: Paul A
authors.initials: PA
authors.lastname: Rota
mesh_terms: D017209:Apoptosis; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D007108:Immune Tolerance; D008459:Measles virus / Q000276:immunology* / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology