Single-cell profiling of peripheral blood reveals acute-phase immune dysregulation in human scrub typhus

Integrated single-cell RNA sequencing, spectral flow cytometry, immune-receptor repertoire profiling, and plasma proteomics revealed coordinated peripheral immune remodeling during acute scrub typhus. Patients exhibited expansion of cytotoxic, clonally amplified CD8⁺ T cells with exhaustion-associated features, depletion and apoptosis of CD4⁺ T cells, B-cell contraction with enhanced plasmablast/plasma-cell differentiation, and inflammatory myeloid remodeling. CD14⁺CXCR6⁺ and CD14⁺GNLY⁺ myeloid-cell frequencies positively correlated with bacterial burden, defining prominent immune features of acute Orientia tsutsugamushi infection.