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

• Published in: Cell 2017-10, Vol.171 (2), p.398-413.e21
• Main Authors: Kadoki, Motohiko, Patil, Ashwini, Thaiss, Cornelius C., Brooks, Donald J., Pandey, Surya, Deep, Deeksha, Alvarez, David, von Andrian, Ulrich H., Wagers, Amy J., Nakai, Kenta, Mikkelsen, Tarjei S., Soumillon, Magali, Chevrier, Nicolas
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Animals; Female; Gene Expression Profiling; Immunologic Memory; Interferon Type I - immunology; Mice; Mice, Inbred C57BL; Organ Specificity; organismal immunology; single-cell analysis; Specific Pathogen-Free Organisms; systems biology; T cell memory; T-Lymphocytes - immunology; vaccines; Vaccinia - immunology; Vaccinia - prevention & control; Vaccinia virus - physiology; Viral Vaccines - administration & dosage; Viral Vaccines - immunology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2017.08.024

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. [Display omitted] •Tracking immunity at the whole-organism scale upon vaccination and viral infection•Type I interferons trigger a whole-body, protective antiviral state within hours•A multi-organ web of tissue-resident memory T cells prevents systemic viral spread•Local adaptations shape the processes targeted by memory T cells in host tissues Tissue-resident memory T cells establish a multi-organ web of communication to stop viral particles from progressing from one tissue to the next.