Human and Mouse Bone Marrow CD45+ Erythroid Cells Have a Constitutive Expression of Antibacterial Immune Response Signature Genes

<b>Introduction</b>: Recent studies have shown that Erythroid progenitor cells exhibit a distinct immunosuppressive and immunoregulatory phenotype associated with the response to bacteria. <b>Methods</b>: The objective of this study was to comprehensively explore the traits of human bone marrow Erythroid cells through protein-protein interaction network analysis using cytokine secretion analysis, and single-cell immunoproteomic analysis using flow cytometry, as well as the re-analysis of publicly available human and mouse bone marrow Erythroid-cell transcriptomic data. <b>Results</b>: Our protein-protein interaction network analysis of human bone marrow Erythroid-cell protein-coding genes identified enrichment in the immune response to lipopolysaccharide, with Calprotectin and Cathepsin G being the main factors. We then mapped the Calprotectin to the CD45⁺ Erythroid cells of both humans and mice via the analysis of the publicly available scRNA-seq data. Additionally, we observed that human bone marrow Erythroid cells secrete cytokines and chemokines, such as IL-1b, IL-8, and IL-18, which are also mainly involved in the immune response to lipopolysaccharide. We also found that human and mouse bone marrow Erythroid-cell conditional media inhibit bacterial growth in vitro. <b>Discussion</b>: These findings suggest that both human and mouse bone marrow CD45⁺ Erythroid cells possess the potential to combat pathogenic microbes and thus play a role in innate antimicrobial immunity. <b>Conclusions</b>: CD45⁺ Erythroid cells are a potent immunoregulatory cell population in both humans and mice.