Phagocytosis deficient glia display phagosome processing defects and macrophage recruitment to the brain of adult Drosophila melanogaster.
Efficient clearance of dying cells is essential for brain homeostasis, yet how partial defects in phagocytic processing affect neuroimmune interactions during aging remains unclear. In the adult Drosophila brain, glia function as professional phagocytes through the conserved engulfment receptor Draper (Drpr). Here, we show that glial loss of Drpr does not completely eliminate phagocytosis but instead leads to persistent, age-dependent inefficiency in corpse degradation. Using a genetically encoded pH-sensitive reporter to visualize acidified phagocytic compartments, we find that drpr-deficient glia retain residual engulfment activity but progressively accumulate enlarged, incompletely degraded phagocytic cargo. This chronic clearance defect coincides with altered immune dynamics at the central nervous system periphery, including increased recruitment and adhesion of peripheral hemocytes at the blood-brain barrier (BBB), without overt BBB disruption. Notably, hemocytes at the brain surface can phagocytose glial material in a Drpr-dependent manner, revealing a form of barrier-associated "border clearance". Together, these findings demonstrate that inefficient corpse degradation is sufficient to reshape neuroimmune interactions during aging. Main pointsO_LIDraper-deficient glia still engulf corpses but fail phagolysososomal degradation. C_LIO_LIImpaired glial clearance reshapes immune dynamics at the CNS periphery. C_LIO_LIWith intact BBB, hemocytes that accumulate on the aging brain surface engulf glial debris. C_LI