RT Journal Article
SR Electronic
T1 Origin and microenvironment contribute to the sexually dimorphic phenotype and function of peritoneal macrophages
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 837336
DO 10.1101/837336
A1 Calum C. Bain
A1 Douglas A. Gibson
A1 Nicholas Steers
A1 Katarina Boufea
A1 Pieter A. Louwe
A1 Catherine Docherty
A1 Victor Huici
A1 Rebecca Gentek
A1 Marlene Magalhaes-Pinto
A1 Marc Bajenoff
A1 Cecile Benezech
A1 David Dockrell
A1 Philippa TK Saunders
A1 Nizar Batada
A1 Stephen J Jenkins
YR 2019
UL http://biorxiv.org/content/early/2019/11/14/837336.abstract
AB Macrophages reside in the body cavities where they maintain serosal homeostasis and provide immune surveillance. Peritoneal macrophages are implicated in the aetiology of pathologies including peritonitis, endometriosis and metastatic cancer thus understanding the factors that govern their behaviour 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 RNAseq revealed striking 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 while others are reliant on local microenvironment signals. Importantly, 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 disease.