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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.

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


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.


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

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