Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control

Mycobacterium tuberculosis lung infection results in a complex multicellular structure: the granuloma. In some granulomas, immune activity promotes bacterial clearance, but in others, bacteria persist and grow. We identified correlates of bacterial control in cynomolgus macaque lung granulomas by co-registering longitudinal positron emission tomography and computed tomography imaging, single-cell RNA sequencing, and measures of bacterial clearance. Bacterial persistence occurred in granulomas enriched for mast, endothelial, fibroblast, and plasma cells, signaling amongst themselves via type 2 immunity and wound-healing pathways. Granulomas that drove bacterial control were characterized by cellular ecosystems…

• NS
  National Science Foundation

  Awards: 1122374, P30-CA14051
• UD
  U.S. Department of Health and Human Services

  Award: 75N93019C00071
• BA
  Bill and Melinda Gates Foundation

  Award: OPP1202327
• UO
  University of Pittsburgh
• WT
  Wellcome Trust
• SS
  Searle Scholars Program
• KI
  Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology

  Award: P30-CA14051
• NI
  National Institutes of Health

  Awards: BAA-NIAID-NIHAI201700104, 75N93019C00071, P30 AI060354, P30-CA14051, NIH K12, R01A1022553, 5U24AI118672, AI060354
• NC
  National Cancer Institute

  Awards: P30-CA14051, CA14051
• NI
  National Institute of Allergy and Infectious Diseases

  Awards: AI060354, BAA-NIAID-NIHAI201700104, 5U24AI118672, 75N93019C00071, R01A1022553, P30 AI060354