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

This is the authors' abstract. We don't add key points for this paper.

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 (CD163 high 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 CD163 high RPMs were mainly self-maintaining. During blood-stage malaria, CD163 high RPMs were rapidly depleted, failed to recover despite parasite clearance, and were replaced by CD163 − monocyte-derived RPMs. Single-cell RNA sequencing and genetic mouse models revealed that CD163 deficiency exacerbated structural disintegration of the marginal zone and selectively impaired marginal metallophilic macrophage (MMM) recovery, underscoring a CD163-dependent RPM-MMM crosstalk. This study reveals that the sustained loss of a specialized, yolk sac-derived CD163 high RPM subset rewires splenic architecture and inter-macrophage crosstalk long after malaria resolution.