Infection history imprints prolonged changes to the epigenome, transcriptome and function of Kupffer cells.

Autor: Musrati MA; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium; Cellular and Molecular Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium., Stijlemans B; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium; Cellular and Molecular Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium., Azouz A; Institute for Medical Immunology, Université Libre de Bruxelles (ULB), Gosselies, Belgium; ULB Center for Research in Immunology (U-CRI), Gosselies, Belgium., Kancheva D; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium; Cellular and Molecular Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium; Brain and Systems Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium., Mesbahi S; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium; Cellular and Molecular Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium., Hadadi E; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium; Cellular and Molecular Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium., Lebegge E; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium; Cellular and Molecular Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium., Ali L; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium; Cellular and Molecular Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium; Brain and Systems Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium., De Vlaminck K; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium; Cellular and Molecular Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium; Brain and Systems Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium., Scheyltjens I; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium; Cellular and Molecular Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium; Brain and Systems Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium., Vandamme N; Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation Research, Ghent, Belgium; VIB Single Cell Core, VIB, Ghent-Leuven, Belgium., Zivalj M; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium; Cellular and Molecular Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium., Assaf N; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium; Cellular and Molecular Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium., Elkrim Y; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium; Cellular and Molecular Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium., Ahmidi I; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium; Cellular and Molecular Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium., Huart C; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium; Cellular and Molecular Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium., Lamkanfi M; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium., Guilliams M; Laboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, VIB-UGent Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Faculty of Sciences, Ghent University, Ghent, Belgium., De Baetselier P; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium; Cellular and Molecular Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium., Goriely S; Institute for Medical Immunology, Université Libre de Bruxelles (ULB), Gosselies, Belgium; ULB Center for Research in Immunology (U-CRI), Gosselies, Belgium., Movahedi K; Brain and Systems Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium. Electronic address: kiavash.movahedi@vub.be., Van Ginderachter JA; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium; Cellular and Molecular Immunology Lab, Brussels Center for Immunology (BCIM), Vrije Universiteit Brussel, Brussels, Belgium. Electronic address: jo.van.ginderachter@vub.be.
Jazyk: angličtina
Zdroj: Journal of hepatology [J Hepatol] 2024 Dec; Vol. 81 (6), pp. 1023-1039. Date of Electronic Publication: 2024 Jul 11.
DOI: 10.1016/j.jhep.2024.07.007
Abstrakt: Background & Aims: Liver macrophages fulfill various homeostatic functions and represent an essential line of defense against pathogenic insults. However, it remains unclear whether a history of infectious disease in the liver leads to long-term alterations to the liver macrophage compartment.
Methods: We utilized a curable model of parasitic infection invoked by the protozoan parasite Trypanosoma brucei brucei to investigate whether infection history can durably reshape hepatic macrophage identity and function. Employing a combination of fate mapping, single-cell CITE-sequencing, single-nuclei multiome analysis, epigenomic analysis, and functional assays, we studied the alterations to the liver macrophage compartment during and after the resolution of infection.
Results: We show that T. brucei brucei infection alters the composition of liver-resident macrophages, leading to the infiltration of monocytes that differentiate into various infection-associated macrophage populations with divergent transcriptomic profiles. Whereas infection-associated macrophages disappear post-resolution of infection, monocyte-derived macrophages engraft in the liver, assume a Kupffer cell (KC)-like profile and co-exist with embryonic KCs in the long-term. Remarkably, the prior exposure to infection imprinted an altered transcriptional program on post-resolution KCs that was underpinned by an epigenetic remodeling of KC chromatin landscapes and a shift in KC ontogeny, along with transcriptional and epigenetic alterations in their niche cells. This reprogramming altered KC functions and was associated with increased resilience to a subsequent bacterial infection.
Conclusion: Our study demonstrates that a prior exposure to a parasitic infection induces trained immunity in KCs, reshaping their identity and function in the long-term.
Impact and Implications: Although the liver is frequently affected during infections, and despite housing a major population of resident macrophages known as Kupffer cells (KCs), it is currently unclear whether infections can durably alter KCs and their niche cells. Our study provides a comprehensive investigation into the long-term impact of a prior, cured parasitic infection, unveiling long-lasting ontogenic, epigenetic, transcriptomic and functional changes to KCs as well as KC niche cells, which may contribute to KC remodeling. Our data suggest that infection history may continuously reprogram KCs throughout life with potential implications for subsequent disease susceptibility in the liver, influencing preventive and therapeutic approaches.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: