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

Authors

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

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.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 08 Jul 2026.

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