Organism-Level Analysis of Vaccination Reveals Networks of Protection across Tissues

Cell. 2017 Oct 5;171(2):398-413.e21. doi: 10.1016/j.cell.2017.08.024. Epub 2017 Sep 21.


A fundamental challenge in immunology is to decipher the principles governing immune responses at the whole-organism scale. Here, using a comparative infection model, we observe immune signal propagation within and between organs to obtain a dynamic map of immune processes at the organism level. We uncover two inter-organ mechanisms of protective immunity mediated by soluble and cellular factors. First, analyzing ligand-receptor connectivity across tissues reveals that type I IFNs trigger a whole-body antiviral state, protecting the host within hours after skin vaccination. Second, combining parabiosis, single-cell analyses, and gene knockouts, we uncover a multi-organ web of tissue-resident memory T cells that functionally adapt to their environment to stop viral spread across the organism. These results have implications for manipulating tissue-resident memory T cells through vaccination and open up new lines of inquiry for the analysis of immune responses at the organism level.

Keywords: T cell memory; organismal immunology; single-cell analysis; systems biology; vaccines.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Female
  • Gene Expression Profiling
  • Immunologic Memory*
  • Interferon Type I / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Organ Specificity
  • Specific Pathogen-Free Organisms
  • T-Lymphocytes / immunology
  • Vaccinia / immunology*
  • Vaccinia / prevention & control*
  • Vaccinia virus / physiology*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology*


  • Interferon Type I
  • Viral Vaccines