This study examined the ontogeny, self-renewal dynamics, and infection-induced fate of splenic CD163-expressing red pulp macrophage (CD163high RPM) subsets in mice, including their role in maintaining marginal zone architecture during and after blood-stage malaria.
CD163high RPMs — derived from yolk sac progenitors and largely self-maintaining — were rapidly depleted during blood-stage malaria and failed to recover post-parasite clearance, being replaced by monocyte-derived CD163− RPMs; CD163 deficiency worsened marginal zone disintegration and impaired marginal metallophilic macrophage (MMM) recovery, revealing a CD163-dependent RPM-MMM crosstalk.
Findings are based on mouse models (fate-mapping and genetic knockouts), limiting direct translation to human malaria; long-term post-infection dynamics were assessed in mice, and it is unclear whether similar subset depletion and non-recovery occur in humans; the study does not address functional immune consequences (e.g., susceptibility to re-infection) of the rewired splenic architecture.
Malaria causes lasting depletion of a specialized yolk sac-derived splenic macrophage subset that does not recover even after parasite clearance, with downstream disruption of marginal zone architecture — clinicians should consider that repeated or severe malaria episodes may cause durable impairment of splenic immune architecture beyond the acute episode.
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