{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE303nnn/GSE303987/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303987"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"CD163 Expression Defines a Red Pulp Macrophage Subset Engaged in Crosstalk with Marginal Metallophilic Macrophages During Blood-Stage Malaria","description":"The spleen harbors distinct macrophage subsets that support circulatory homeostasis and initiate immune responses. Yet, the ontogeny and long-term dynamics of these populations remain incompletely understood. Here, we identify a transcriptionally and developmentally distinct CD163-expressing red pulp macrophage (CD163high RPM) population that arises from yolk sac progenitors and maintains CD163 expression under homeostatic conditions. Using fate-mapping models, we show that CD163- RPMs are progressively replenished by monocytes during ageing, whereas CD163high RPMs are rather self-maintaining and occupy a vascular-associated niche. During blood-stage malaria, CD163high RPMs are rapidly depleted and fail to recover despite clearance of parasitemia. Mechanistically, the loss of CD163 expression is driven by infection-induced hemolysis and iron depletion, not parasite persistence. Single-cell RNA sequencing reveals that CD163high RPMs act as dominant signaling hubs under steady state, but malaria disrupts these intercellular communication networks, including a previously unrecognized interaction with marginal metallophilic macrophages (MMMs). CD163 deficiency exacerbates structural disintegration of the marginal zone and selectively impairs MMM recovery, underscoring a CD163-dependent regulatory axis between RPMs and MMMs. This study provides a comprehensive ontogenetic and functional map of splenic macrophages, and reveals that the sustained loss of a specialized, yolk sac-derived CD163high RPM subset rewires splenic architecture and inter-macrophage crosstalk long after infection resolution.","dates":{"publication":"2026/07/28"},"accession":"GSE303987","cross_references":{"GSM":["GSM9140400","GSM9140405","GSM9140406","GSM9140407","GSM9140401","GSM9140402","GSM9140403","GSM9140404"],"GPL":["30172"],"GSE":["303987"],"taxon":["Mus musculus"]}}