CD163 red pulp macrophages interact with marginal metallophilic macrophages during blood-stage malaria to maintain splenic architecture.

Abstract

The spleen harbors distinct macrophage subsets that support circulatory homeostasis and initiate immune responses, but the ontogeny and long-term dynamics of these populations remain incompletely understood. Here, we identified a transcriptionally and developmentally distinct CD163-expressing red pulp macrophage (CD163high RPM) population that arose from yolk sac progenitors and occupied a vascular-associated niche. Using fate-mapping models, we showed that CD163- RPMs were progressively replenished by monocytes during aging, whereas CD163high RPMs were mainly self-maintaining. During blood-stage malaria, CD163high RPMs were rapidly depleted, failed to recover despite parasite clearance, and..