Role of Dendritic Cells in Differential Susceptibility to Viral Demyelinating Disease

PLoS Pathogens

Wanqiu Hou¹  Byung S Kim¹  Eui Young So¹ 

[1] Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America

关键词: T cells;    Cytokines;    Viral transmission;    infection;    Viral persistence;    latency;    Cell staining;    Central nervous system;    Apoptosis;    Immune response;   

DOI  :  10.1371/journal.ppat.0030124

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Although persistent viral diseases are a global health concern, the mechanisms of differential susceptibility to such infections among individuals are unknown. Here, we report that differential interactions between dendritic cells (DCs) and virus are critical in determining resistance versus susceptibility in the Theiler murine encephalomyelitis virus–induced demyelinating disease model of multiple sclerosis. This virus induces a chronic demyelinating disease in susceptible mice, whereas the virus is completely cleared in resistant strains of mice. DCs from susceptible mice are more permissive to viral infection, resulting in severe deficiencies in development, expansion, and function, in contrast to DCs from resistant mice. Although protective prior to viral infection, higher levels of type I interferons (IFNs) and IFN-γ produced by virus-infected DCs from susceptible mice further contribute to the differential inhibition of DC development and function. An increased DC number and/or acquired resistance of DCs to viral infection render susceptible mice resistant to viral persistence and disease progression. Thus, the differential permissiveness of DCs to infectious agents and its subsequent functional and developmental deficiencies determine the outcome of infection- associated diseases. Therefore, arming DCs against viral infection–induced functional decline may provide a useful intervention for chronic infection-associated diseases.

【 授权许可】

CC BY