ABSTRACT Schistosoma mansoni infection induces marked splenic remodelling, but the phenotype of macrophages driving this process remains unclear. CD163 is frequently used as an M2‐associated marker in chronic helminth infections. This study evaluated whether the CD163:CD68 ratio can serve as a semi‐quantitative indicator of macrophage polarisation in schistosomal splenomegaly. Forty female CD‐1 mice were divided into infected and control groups, and spleens were collected at 7‐, 15‐, and 23‐weeks post‐infection. Histopathology and immunohistochemistry for CD68 and CD163 were quantified in five high‐power fields per animal. Semi‐quantitative scoring, percentage positivity, CD163:CD68 ratios, and correlations with pathological severity were analysed. Chronic infection caused progressive splenic pathology, including white pulp atrophy, red pulp congestion, fibrous septa, extramedullary haematopoiesis, and hemosiderin‐laden macrophages. CD68 + macrophages increased significantly from 20% to 30% in controls to 70%–85% at 23 weeks ( p < 0.001), while CD163 expression declined from 49.3% in naïve spleens to nearly zero at all post‐infection time points. The CD163:CD68 ratio fell from 1.97 to near zero. CD163 correlated negatively with CD68 ( ρ = −0.891) and pathology severity ( ρ = −0.876), whereas CD68 showed a strong positive correlation ( ρ = +0.912). Chronic S. mansoni infection induces a profound, early, and sustained downregulation of CD163 expression on splenic macrophages despite expansion of the total macrophage pool. While CD163 loss associates with splenic congestion, iron accumulation, and architectural remodelling, the functional implications of this change remain to be fully defined. We therefore propose that disruption of CD163‐dependent homeostatic programmes may contribute to splenic pathology, a hypothesis that warrants future functional and multi‐marker validation in line with current concepts of macrophage plasticity.
Ammar et al. (2026) studied this question.