biostudies-literatureGideon HPNIAID NIH HHSNHLBI NIH HHSNCI NIH HHSWellcome TrustNIGMS NIH HHS827-846.e10https://www.ebi.ac.uk/biostudies/studies/S-EPMC9122264biostudies-literatureUnknown55(5)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 enriched for type 1-type 17, stem-like, and cytotoxic T cells engaged in pro-inflImmunityMultimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control.PMC9122264T32 GM087237R01 AI022553P30 AI060354210662/Z/16/ZU01 HL157004K12 HL143886P30 CA014051U24 AI118672T32 AI007387F30 AI143160T32 AI065380Flynn JLBehar SMMyers AAmeel CLFortune SMTomko JACochran CTMadansein RWhite AGHopkins FFNargan KChao MPeters JMMaiello PHughes TKTzouanas CNBryson BLeslie AGrant NLBerger BLin PLGanchua SKCOrdovas-Montanes JWadsworth MHTu AAScanga CAGideon HPMattila JTPatel KVRosenberg JMNyquist SKKlein EFrye LJShalek AKBorish HJLove JCWei JRPhuah JYShih AWinchell CGIbrahim SGierahn TMKummerlowe CfalseMultimodal 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 enriched for type 1-type 17, stem-like, and cytotoxic T cells engaged in pro-infl2022-01-01T00:00:00Z2022 May2026-05-10T01:38:56.771Z2025-02-19T01:12:31.689ZS-EPMC91222643548335510.1016/j.immuni.2022.04.004