CXCL10<sup>high</sup> Microglia in Cerebral Malaria: Toward Translational Validation
Abstract
Wang et al. identify CXCL10<sup>high</sup> TNFα<sup>high</sup> Ki67<sup>+</sup> microglia as drivers of CD8<sup>+</sup> T cell recruitment during experimental cerebral malaria (ECM). We propose a conservative reframing: rather than asserting a fully validated new taxonomy, CXCL10<sup>high</sup> microglia should be considered a candidate "neuroimmune endotype" whose translational relevance requires clearly prespecified and testable validation in human disease. Priority validation steps include single-nucleus and spatial transcriptomics of human postmortem tissue, paired plasma/CSF biomarker correlation, and mechanistic assays of microglial antigen presentation. We caution against strong therapeutic inferences from ECM alone; translational work should first establish reproducible human microglial signatures and clinical correlations before precision-targeted interventions are proposed.