Linking cell dynamics with gene coexpression networks to characterize key events in chronic virus infections

Mireia Pedragosa, Graciela Riera, Valentina Casella, Anna Esteve-Codina, Yael Steuerman, Celina Seth, Gennady Bocharov, Simon Heath, Irit Gat-Viks, Jordi Argilaguet, Andreas Meyerhans*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The host immune response against infection requires the coordinated action of many diverse cell subsets that dynamically adapt to a pathogen threat. Due to the complexity of such a response, most immunological studies have focused on a few genes, proteins, or cell types. With the development of “omic”-technologies and computational analysis methods, attempts to analyze and understand complex system dynamics are now feasible. However, the decomposition of transcriptomic data sets generated from complete organs remains a major challenge. Here, we combined Weighted Gene Coexpression Network Analysis (WGCNA) and Digital Cell Quantifier (DCQ) to analyze time-resolved mouse splenic transcriptomes in acute and chronic Lymphocytic Choriomeningitis Virus (LCMV) infections. This enabled us to generate hypotheses about complex immune functioning after a virus-induced perturbation. This strategy was validated by successfully predicting several known immune phenomena, such as effector cytotoxic T lymphocyte (CTL) expansion and exhaustion. Furthermore, we predicted and subsequently verified experimentally macrophage-CD8 T cell cooperativity and the participation of virus-specific CD8+ T cells with an early effector transcriptome profile in the host adaptation to chronic infection. Thus, the linking of gene expression changes with immune cell kinetics provides novel insights into the complex immune processes within infected tissues.

Original languageEnglish
Article number1002
JournalFrontiers in Immunology
Volume10
Issue numberMAY
DOIs
StatePublished - 2019

Keywords

  • Cell dynamics
  • Chronic infection
  • Coexpression networks
  • DCQ
  • LCMV
  • Systems biology
  • WGCNA

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