Systems analysis reveals complex biological processes during virus infection fate decisions
- Jordi Argilaguet1,
- Mireia Pedragosa1,
- Anna Esteve-Codina2,
- Graciela Riera1,
- Enric Vidal3,
- Cristina Peligero-Cruz4,
- Valentina Casella1,
- David Andreu1,
- Tsuneyasu Kaisho5,
- Gennady Bocharov6,
- Burkhard Ludewig7,
- Simon Heath2 and
- Andreas Meyerhans1,8
- 1 Universitat Pompeu Fabra;
- 2 Barcelona Institute of Science and Technology;
- 3 IRTA, Centre de Recerca en Sanitat Animal;
- 4 Weizmann Institute of Science;
- 5 Wakayama Medical University, Institute of Advanced Medicine;
- 6 Marchuk Institute of Numerical Mathematics, Russian Academy of Sciences;
- 7 Kantonsspital St. Gallen, Institute for Immunobiology
Abstract
The processes and mechanisms of virus infection fate decisions that are the result of a dynamic virus-immune system interaction with either an efficient effector response and virus elimination or an alleviated immune response and chronic infection are poorly understood. Here we characterized the host response to acute and chronic lymphocytic choriomeningitis virus (LCMV) infections by gene coexpression network analysis of time-resolved splenic transcriptomes. 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 chronic infection phase.
- Received July 3, 2018.
- Accepted May 14, 2019.
- Published by Cold Spring Harbor Laboratory Press
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