Commensal-driven immune zonation of the liver promotes host defence.

Autor: Gola A; Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. agola@rockefeller.edu.; Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY, USA. agola@rockefeller.edu., Dorrington MG; Signaling Systems Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Speranza E; Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Innate Immunity and Pathogenesis Section, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Sala C; Department of Physics and Astronomy, University of Bologna, Bologna, Italy., Shih RM; Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Radtke AJ; Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Wong HS; Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Baptista AP; Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium., Hernandez JM; Metastasis Biology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Castellani G; Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy., Fraser IDC; Signaling Systems Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Germain RN; Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. rgermain@niaid.nih.gov.
Jazyk: angličtina
Zdroj: Nature [Nature] 2021 Jan; Vol. 589 (7840), pp. 131-136. Date of Electronic Publication: 2020 Nov 25.
DOI: 10.1038/s41586-020-2977-2
Abstrakt: 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.
Databáze: MEDLINE
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