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Isolation of Mouse Lung Dendritic Cells
Published on: November 22, 2011
Dendritic cell subsets involved in type I IFN induction in mouse measles virus infection models
Hiromi Takaki1, Hiroyuki Oshiumi1, Misako Matsumoto1
1Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, Japan.
Abstract:
Measles caused by measles virus (MV) infection remains important in child mortality. Although the natural host of MV is human, mouse models expressing MV entry receptors (human CD46, CD150) and disrupting the interferon (IFN) pathways work for investigating immune responses during early MV infection in vivo. Dendritic cells (DCs) are primary targets for MV in the mouse models and are efficiently infected with several MV strains in the respiratory tract in vivo. However, questions remain about what kind of DC in a variety of DC subsets is involved in initial MV infection and how the RNA sensors evoke circumventing signals against MV in infected DCs. Since type I IFN-inducing pathways are a pivotal defense system that leads to the restriction of systemic viral infection, we have generated CD150-transgenic mice with disrupting each of the IFN-inducing pathway, and clarified that DC subsets had subset-specific IFN-inducing systems, which critically determined the DC's differential susceptibility to MV.
Insights
Measles virus infects dendritic cells (DCs), crucial immune cells. This study reveals subset-specific interferon pathways in DCs, determining their susceptibility to measles virus (MV) infection in mice.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Measles virus (MV) remains a significant cause of child mortality.
- Mouse models are essential for studying MV infection and immune responses.
- Dendritic cells (DCs) are primary targets for MV in these models, particularly in the respiratory tract.
Purpose of the Study:
- To identify specific dendritic cell (DC) subsets involved in initial measles virus (MV) infection.
- To investigate how RNA sensors and interferon (IFN) pathways in DCs respond to MV.
- To understand the role of type I IFN-inducing pathways in DC susceptibility to MV.
Main Methods:
- Generation of CD150-transgenic mice with disrupted interferon-inducing pathways.
- In vivo infection models to study MV entry and replication in DCs.
- Analysis of DC subset-specific responses to MV infection.
Main Results:
- Dendritic cell (DC) subsets exhibit distinct interferon (IFN)-inducing pathway systems.
- These subset-specific IFN systems critically influence the differential susceptibility of DCs to measles virus (MV).
- Identified specific DC subsets involved in the initial stages of MV infection.
Conclusions:
- Dendritic cell (DC) subset-specific interferon (IFN) responses are key determinants of measles virus (MV) susceptibility.
- Understanding these pathways is crucial for developing effective antiviral strategies against MV.
- This research clarifies the complex interplay between MV, DCs, and innate immunity.
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