Rate of replenishment and microenvironment contribute to the sexually dimorphic phenotype and function of peritoneal macrophages.

Autor:	Bain CC; University of Edinburgh Centre for Inflammation Research, Queens Medical Research Institute, Edinburgh EH16 4TJ, UK. calum.bain@ed.ac.uk stephen.jenkins@ed.ac.uk., Gibson DA; University of Edinburgh Centre for Inflammation Research, Queens Medical Research Institute, Edinburgh EH16 4TJ, UK., Steers NJ; Columbia University Irving Medical Center, Columbia University, New York, NY 10032, USA., Boufea K; Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK., Louwe PA; University of Edinburgh Centre for Inflammation Research, Queens Medical Research Institute, Edinburgh EH16 4TJ, UK., Doherty C; University of Edinburgh Centre for Inflammation Research, Queens Medical Research Institute, Edinburgh EH16 4TJ, UK., González-Huici V; Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK., Gentek R; Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, 13288 Marseille, France., Magalhaes-Pinto M; Lydia Becker Institute for Immunology and Infection, Faculty of Biology, Medicine and Health, Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK., Shaw T; Lydia Becker Institute for Immunology and Infection, Faculty of Biology, Medicine and Health, Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK.; Manchester Collaborative Centre for Inflammation Research (MCCIR), University of Manchester, Manchester, UK., Bajénoff M; Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, 13288 Marseille, France., Bénézech C; Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh EH16 4TJ, UK., Walmsley SR; University of Edinburgh Centre for Inflammation Research, Queens Medical Research Institute, Edinburgh EH16 4TJ, UK., Dockrell DH; University of Edinburgh Centre for Inflammation Research, Queens Medical Research Institute, Edinburgh EH16 4TJ, UK., Saunders PTK; University of Edinburgh Centre for Inflammation Research, Queens Medical Research Institute, Edinburgh EH16 4TJ, UK., Batada NN; Institute for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK., Jenkins SJ; University of Edinburgh Centre for Inflammation Research, Queens Medical Research Institute, Edinburgh EH16 4TJ, UK. calum.bain@ed.ac.uk stephen.jenkins@ed.ac.uk.
Jazyk:	angličtina
Zdroj:	Science immunology [Sci Immunol] 2020 Jun 19; Vol. 5 (48).
DOI:	10.1126/sciimmunol.abc4466
Abstrakt:	Macrophages reside in the body cavities where they maintain serosal homeostasis and provide immune surveillance. Peritoneal macrophages are implicated in the etiology of pathologies including peritonitis, endometriosis, and metastatic cancer; thus, understanding the factors that govern their behavior is vital. Using a combination of fate mapping techniques, we have investigated the impact of sex and age on murine peritoneal macrophage differentiation, turnover, and function. We demonstrate that the sexually dimorphic replenishment of peritoneal macrophages from the bone marrow, which is high in males and very low in females, is driven by changes in the local microenvironment that arise upon sexual maturation. Population and single-cell RNA sequencing revealed marked dimorphisms in gene expression between male and female peritoneal macrophages that was, in part, explained by differences in composition of these populations. By estimating the time of residency of different subsets within the cavity and assessing development of dimorphisms with age and in monocytopenic Ccr2 -/- mice, we demonstrate that key sex-dependent features of peritoneal macrophages are a function of the differential rate of replenishment from the bone marrow, whereas others are reliant on local microenvironment signals. We demonstrate that the dimorphic turnover of peritoneal macrophages contributes to differences in the ability to protect against pneumococcal peritonitis between the sexes. These data highlight the importance of considering both sex and age in susceptibility to inflammatory and infectious diseases. (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze:	MEDLINE
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