Commensal-driven immune zonation of the liver promotes host defence

被引：180

作者：

Gola, Anita ^{[1
,9
]}

Dorrington, Michael G. ^{[2
]}

Speranza, Emily ^{[1
,3
]}

Sala, Claudia ^{[4
]}

Shih, Rochelle M. ^{[1
]}

Radtke, Andrea J. ^{[1
]}

Wong, Harikesh S. ^{[1
]}

Baptista, Antonio P. ^{[1
,5
,6
]}

Hernandez, Jonathan M. ^{[7
]}

Castellani, Gastone ^{[8
]}

Fraser, Iain D. C. ^{[2
]}

Germain, Ronald N. ^{[1
]}

机构：

[1] NIH, NIAID, Lab Immune Syst Biol, Lymphocyte Biol Sect, Bldg 10, Bethesda, MD 20892 USA

[2] NIH, NIAID, Lab Immune Syst Biol, Signaling Syst Sect, Bldg 10, Bethesda, MD 20892 USA

[3] NIH, NIAID, Lab Virol, Innate Immun & Pathogenesis Sect, Bldg 10, Bethesda, MD 20892 USA

[4] Univ Bologna, Dept Phys & Astron, Bologna, Italy

[5] VIB, UGent Ctr Inflammat Res, Lab Immunoregulat & Mucosal Immunol, Ghent, Belgium

[6] Univ Ghent, Dept Internal Med & Pediat, Ghent, Belgium

[7] NIH, NCI, Ctr Canc Res, Metastasis Biol Sect, Bethesda, MD USA

[8] Univ Bologna, Dept Expt Diagnost & Specialty Med, Bologna, Italy

[9] Rockefeller Univ, Lab Mammalian Cell Biol & Dev, 1230 York Ave, New York, NY 10021 USA

来源：

NATURE | 2021年 / 589卷 / 7840期

关键词：

NKT CELLS; EXPRESSION; GENE; LYMPHOCYTES; MULTIPLEX; INNATE;

D O I：

10.1038/s41586-020-2977-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The authors show that zonation extends to hepatic immune cells and that this spatial patterning is mediated by microbiome sensing by liver sinusoidal endothelial cells, and provide evidence that immune zonation is required to protect the host from the dissemination of blood-borne pathogens. The liver connects the intestinal portal vasculature with the general circulation, using a diverse array of immune cells to protect from pathogens that translocate from the gut(1). In liver lobules, blood flows from portal triads that are situated in periportal lobular regions to the central vein via a polarized sinusoidal network. Despite this asymmetry, resident immune cells in the liver are considered to be broadly dispersed across the lobule. This differs from lymphoid organs, in which immune cells adopt spatially biased positions to promote effective host defence(2,3). Here we used quantitative multiplex imaging, genetic perturbations, transcriptomics, infection-based assays and mathematical modelling to reassess the relationship between the localization of immune cells in the liver and host protection. We found that myeloid and lymphoid resident immune cells concentrate around periportal regions. This asymmetric localization was not developmentally controlled, but resulted from sustained MYD88-dependent signalling induced by commensal bacteria in liver sinusoidal endothelial cells, which in turn regulated the composition of the pericellular matrix involved in the formation of chemokine gradients. In vivo experiments and modelling showed that this immune spatial polarization was more efficient than a uniform distribution in protecting against systemic bacterial dissemination. Together, these data reveal that liver sinusoidal endothelial cells sense the microbiome, actively orchestrating the localization of immune cells, to optimize host defence.

引用

页码：131 / U285

页数：31

共 42 条

[1] spatstat: An R package for analyzing spatial point patterns [J].