High Dimensional Immune Profiling Reveals CD39 as a Correlate of Tuberculosis Disease Severity

Watt, J.; Sokolowski, D. J.; Xu, W.; Quan, Y.; Burrows, K.; Galutira, J.; Gordon, B.; Brooks, D. G.; Liu, J.

doi:10.64898/2026.07.01.735885

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bioRxiv · 10.64898/2026.07.01.735885

High Dimensional Immune Profiling Reveals CD39 as a Correlate of Tuberculosis Disease Severity

Watt, J.·Sokolowski, D. J.·Xu, W.·Quan, Y.·Burrows, K.·Galutira, J.·Gordon, B.·Brooks, D. G.·Liu, J.

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Abstract

Immune biomarkers of tuberculosis (TB) disease severity present a challenging area of research that remains poorly understood. New technologies are able to perform larger, unbiased studies that can unravel the complex host-pathogen dynamics occurring during a Mycobacterium tuberculosis infection, the causative agent of TB. In this study, we designed a high dimensional approach combining viable bacterial burden (CFU, colony forming units) with time-of-flight mass cytometry (CyTOF) analysis to profile differences in cell-type abundance and cell-type specific protein expression during states of low, intermediate and high TB disease burden. Broadly, we segregated cell-type specific immune responses into those driven by bacterial burden and/or the mycobacterial infection strain. Interrogating these immune signatures allowed us to identify ATP-catabolizing protein CD39 as a correlate of disease severity. Treatment of mice with a small molecule inhibitor of CD39 promoted effector T cell functions and CD4 T cell expansion during Mtb infection. Collectively, our data defines the differential lung immune environment between various mycobacterial disease severity states and uncovers a potential immune biomarker of infection and therapeutic immunomodulating target to aid in the treatment of TB.

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Watt, J., Sokolowski, D. J., Xu, W., Quan, Y., Burrows, K., Galutira, J., Gordon, B., Brooks, D. G., Liu, J.. 2026-07-07. High Dimensional Immune Profiling Reveals CD39 as a Correlate of Tuberculosis Disease Severity. https://doi.org/10.64898/2026.07.01.735885

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