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

doi:10.1016/j.cell.2017.08.024

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

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

66 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 language	English (US)
Pages (from-to)	398-413.e21
Journal	Cell
Volume	171
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2017.08.024
State	Published - Oct 5 2017

Funding

We thank the members of the FAS Center for Systems Biology, Diane Mathis, Douglas Melton, David Knipe, William Heath, Laura Mackay, and Akiko Iwasaki for valuable discussions; Andrew Murray, Philippe Cluzel, Sean Eddy, and Peter Sage for critically reading the manuscript; the New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases (NERCE) core; Christine Anderson, and John Connor for help with virus handling; Joyce LaVecchio and Silvia Ionescu for help with FACS; Christian Daly and Claire Reardon for help with sequencing; Andreas Sjodin, Rory Kirchner, John Hutchinson, and Shannan Ho Sui for help with bioinformatics; David Ginty and Emily Kuehn for help with whole-mount skin immunostaining; Douglas Richardson for help with imaging; Allon Klein and Alex Ratner for help with inDrops; Tian Tian and Thomas Kupper for help with viral DNA qPCR; Harvard University FAS Research Computing and University of Tokyo Human Genome Center for computing resources; and MCB graphics and Sigrid Knemeyer for help with artwork. This work was supported by a Grant-in-Aid for Young Scientists (26830135) by the Japan Society for the Promotion of Science (A.P.), and the Bauer Fellows Program, the William F. Milton Fund, and the Harvard University Center for AIDS Research (NIH/NIAID 5P30AI060354-12) (N.C.). We thank the members of the FAS Center for Systems Biology, Diane Mathis, Douglas Melton, David Knipe, William Heath, Laura Mackay, and Akiko Iwasaki for valuable discussions; Andrew Murray, Philippe Cluzel, Sean Eddy, and Peter Sage for critically reading the manuscript; the New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases (NERCE) core; Christine Anderson, and John Connor for help with virus handling; Joyce LaVecchio and Silvia Ionescu for help with FACS; Christian Daly and Claire Reardon for help with sequencing; Andreas Sjodin, Rory Kirchner, John Hutchinson, and Shannan Ho Sui for help with bioinformatics; David Ginty and Emily Kuehn for help with whole-mount skin immunostaining; Douglas Richardson for help with imaging; Allon Klein and Alex Ratner for help with inDrops; Tian Tian and Thomas Kupper for help with viral DNA qPCR; Harvard University FAS Research Computing and University of Tokyo Human Genome Center for computing resources; and MCB graphics and Sigrid Knemeyer for help with artwork. This work was supported by a Grant-in-Aid for Young Scientists (26830135) by the Japan Society for the Promotion of Science (A.P.), and the Bauer Fellows Program , the William F. Milton Fund , and the Harvard University Center for AIDS Research ( NIH/NIAID 5P30AI060354-12 ) (N.C.).

Keywords

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

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cell.2017.08.024

Cite this

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title = "Organism-Level Analysis of Vaccination Reveals Networks of Protection across Tissues",

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.",

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AU - Deep, Deeksha

AU - Alvarez, David

AU - von Andrian, Ulrich H.

AU - Wagers, Amy J.

AU - Nakai, Kenta

AU - Mikkelsen, Tarjei S.

AU - Soumillon, Magali

AU - Chevrier, Nicolas

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AB - 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.

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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