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Microarray analysis of splenic reservoir monocytes and their blood counterparts

ABSTRACT: A current paradigm states that monocytes circulate freely and patrol blood vessels, but differentiate irreversibly into dendritic cells or macrophages upon tissue entry. Here we show that bona fide undifferentiated monocytes reside in the spleen and outnumber their equivalents in circulation. The reservoir monocytes are relatively immotile, assemble in clusters in the cords of the subcapsular red pulp, and are distinct from macrophages and dendritic cells. In response to ischemic myocardial injury, splenic monocytes increase their motility, exit the spleen en masse, accumulate in injured tissue and participate in wound healing. These observations uncover a role for the spleen as a site for storage and rapid deployment of monocytes, and identify the splenic monocyte reservoir as a resource that the body exploits to regulate inflammation. The goal of this gene expression study was to compare the gene expression of Ly-6C hi inflammatory monocytes residing in the spleen and their circulating counterparts in the blood.

ORGANISM(S): Mus musculus

PROVIDER: GSE14850 | GEO | 2009/08/03

SECONDARY ACCESSION(S): PRJNA112129

REPOSITORIES: GEO

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Project description:The spleen is a conserved secondary lymphoid organ that emerged in parallel to adaptive immunity in early jawed vertebrates. Recent studies have applied single cell transcriptomics to reveal the cellular composition of spleen in several species, cataloguing diverse immune cell types and subpopulations. In this study, 51,119 spleen nuclei transcriptomes were comprehensively investigated in the commercially important teleost Atlantic salmon (Salmo salar L.), contrasting control animals with those challenged with the bacterial pathogen Aeromonas salmonicida. We identified clusters of nuclei representing the expected major cell types, namely T cells, B cells, natural killer-like cells, granulocytes, mononuclear phagocytes, endothelial cells, mesenchymal cells, erythrocytes and thrombocytes. We discovered heterogeneity within several immune lineages, providing evidence for resident macrophages and melanomacrophages, infiltrating monocytes, several candidate dendritic cell subpopulations, and B cells at distinct stages of differentiation, including plasma cells and an igt+ B subset. We provide evidence for twelve candidate T cell subsets, including cd4+ T helper and regulatory T cells, one cd8+ subset, three γδT subsets, and populations double negative for cd4 and cd8. The number of genes showing differential expression during the early stages of infection with Aeromonas was highly variable across cell types, with the largest changes observed in resident macrophages and infiltrating monocytes, followed by resting mature B cells. Our differential expression analysis offers evidence for a strong inflammatory response to bacteria in the spleen driven by macrophages and monocytes, and the recruitment of splenic igt+ B cells to the gut. Overall, this study provides a new cell-resolved perspective of the immune actions of Atlantic salmon spleen, highlighting extensive heterogeneity hidden to bulk transcriptomics. We further provide a large catalogue of cell-specific marker genes that can be leveraged to further explore the function and structural organization of the salmonid immune system.

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Microarray analysis of splenic reservoir monocytes and their blood counterparts

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