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

Motohiko Kadoki, Ashwini Patil, Cornelius C. Thaiss, Donald J. Brooks, Surya Pandey, Deeksha Deep, David Alvarez, Ulrich H. von Andrian, Amy J. Wagers, Kenta Nakai, Tarjei S. Mikkelsen, Magali Soumillon, Nicolas Chevrier*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

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. Tissue-resident memory T cells establish a multi-organ web of communication to stop viral particles from progressing from one tissue to the next.

Original languageEnglish (US)
Pages (from-to)398-413.e21
JournalCell
Volume171
Issue number2
DOIs
StatePublished - Oct 5 2017

Keywords

  • T cell memory
  • organismal immunology
  • single-cell analysis
  • systems biology
  • vaccines

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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