Measles virus suppresses cell-mediated immunity by interfering with the survival and functions of dendritic and T cells
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I Fugier-Vivier1, C Servet-Delprat, P Rivailler
1Laboratory for Immunological Research, Schering-Plough, Dardilly, France.
Abstract:
Secondary infections due to a marked immunosuppression have long been recognized as a major cause of the high morbidity and mortality rate associated with acute measles. The mechanisms underlying the inhibition of cell-mediated immunity are not clearly understood but dysfunctions of monocytes as antigen-presenting cells (APC) are implicated. In this report, we demonstrate that measles virus (MV) replicates weakly in the resting dendritic cells (DC) as in lipopolysaccharide-activated monocytes, but intensively in CD40-activated DC. The interaction of MV-infected DC with T cells not only induces syncytia formation where MV undergoes massive replication, but also leads to an impairment of DC and T cell function and cell death. CD40-activated DC decrease their capacity to produce interleukin (IL) 12, and T cells are unable to proliferate in response to MV-infected DC stimulation. A massive apoptosis of both DC and T cells is observed in the MV pulsed DC-T cell cocultures. This study suggests that DC represent a major target of MV. The enhanced MV replication during DC-T cell interaction, leading to an IL-12 production decrease and the deletion of DC and T cells, may be the essential mechanism of immunosuppression induced by MV.
Insights
Measles virus (MV) targets dendritic cells (DCs), impairing their function and leading to T cell death. This interaction causes immunosuppression, increasing measles morbidity and mortality.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Measles causes high morbidity and mortality, partly due to secondary infections from immunosuppression.
- The mechanisms of measles-induced immunosuppression, particularly involving antigen-presenting cells (APCs), are not fully understood.
Purpose of the Study:
- To investigate the role of dendritic cells (DCs) in measles virus (MV)-induced immunosuppression.
- To elucidate the interaction between MV-infected DCs and T cells.
Main Methods:
- Assessing MV replication in resting and activated dendritic cells (DCs) and monocytes.
- Analyzing the interaction between MV-infected DCs and T cells in co-cultures.
- Measuring DC function (IL-12 production) and T cell proliferation.
- Observing apoptosis in co-cultured DC and T cells.
Main Results:
- MV replicates intensively in CD40-activated DCs, but weakly in resting DCs and activated monocytes.
- MV-infected DCs impair T cell function, reduce IL-12 production, and induce syncytia formation.
- Co-culture of MV-infected DCs and T cells leads to massive apoptosis of both cell types.
Conclusions:
- Dendritic cells (DCs) are a major target for measles virus (MV).
- Enhanced MV replication in DCs during DC-T cell interaction contributes to immunosuppression.
- Reduced IL-12 production and apoptosis of DCs and T cells are key mechanisms of MV-induced immune dysfunction.