CD163 Expression Defines a Red Pulp Macrophage Subset Engaged in Crosstalk with Marginal Metallophilic Macrophages During Blood-Stage Malaria

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.