DOI: 10.1101/476077Nov 22, 2018Paper

Time-resolved systems analysis reveals a critical role of XCR1+ 1 dendritic cells in the maintenance of effector T cells during chronic viral infection

BioRxiv : the Preprint Server for Biology
Jordi ArgilaguetAndreas Meyerhans


Upon a viral infection, the host immune system attempts to eradicate the virus. However, once the infection threat seems overwhelming, the infected host actively shuts down effector responses to reduce immunopathology. The price to pay for this is the establishment of a chronic infection that is only partially controlled by a lower level immune response. The genetic networks underlying this infection fate decision and the immune adaptation to the lower level response are not well understood. Here we used an integrated approach of gene coexpression network analysis of time-resolved splenic transcriptomes and immunological analysis to characterize the host response to acute and chronic lymphocytic choriomeningitis virus (LCMV) infections. We found first, an early attenuation of inflammatory monocyte/macrophage prior to the onset of T cell exhaustion and second, a critical role of the XCL1-XCR1 communication axis during the functional adaptation of the T cell response to the chronic infection state. These findings not only reveal an important feedback mechanism that couples T cell exhaustion with the maintenance of a lower level of effector T cell response but also suggest therapy options to better control virus levels during the ...Continue Reading

Related Concepts

Dendritic Cells
Gene Expression
Lymphocytic Choriomeningitis
Virus Diseases
Chronic Infectious Disease
CCXCR1 receptor, human
Immune Response

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