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

被引：69

作者：

Kadoki, Motohiko ^{[1
]}

Patil, Ashwini ^{[3
]}

Thaiss, Cornelius C. ^{[1
]}

Brooks, Donald J. ^{[1
]}

Pandey, Surya ^{[1
,5
]}

Deep, Deeksha ^{[1
]}

Alvarez, David ^{[4
]}

von Andrian, Ulrich H. ^{[4
]}

Wagers, Amy J. ^{[2
]}

Nakai, Kenta ^{[3
]}

Mikkelsen, Tarjei S. ^{[2
]}

Soumillon, Magali ^{[2
]}

Chevrier, Nicolas ^{[1
,5
]}

机构：

[1] Harvard Univ, Ctr Syst Biol, Fac Arts & Sci, Cambridge, MA 02138 USA

[2] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[3] Univ Tokyo, Inst Med Sci, Human Genome Ctr, Tokyo 1088639, Japan

[4] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA

[5] Univ Chicago, Inst Mol Engn, Chicago, IL 60637 USA

来源：

CELL | 2017年 / 171卷 / 02期

基金：

日本学术振兴会;

关键词：

CD8(+) T-CELLS; RESIDENT MEMORY; GENE-EXPRESSION; PROGRAM; VIRUS; DIFFERENTIATION; INFECTION; MIGRATION; GENOME; READS;

D O I：

10.1016/j.cell.2017.08.024

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：398 / +

页数：37

共 75 条

[1]

Cutting Edge: Intravascular Staining Redefines Lung CD8 T Cell Responses [J].