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

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

Author information

1
Faculty of Arts & Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.
2
Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
3
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
4
Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
5
Faculty of Arts & Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: nchevrier@uchicago.edu.

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.

KEYWORDS:

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

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PMID:
28942919
DOI:
10.1016/j.cell.2017.08.024
[Indexed for MEDLINE]
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