Hughes et al. find that the TB susceptibility gene lta4h contributes to the recruitment and differentiation of a discrete set of fibroblasts that populate the periphery of mycobacterial granulomas in ...

Using macroevolution, species not strains, uncovered important diversity in how mycobacteria respond to and resist antibiotics, revealing novel resistance determinants.

Sarcoidosis is a systemic, inflammatory disease defined by the presence of noncaseating granulomas in affected organs. Single-cell and spatial profiling have resolved granulomas to be highly ordered s...

A collection of antigen-stabilizable fluorescent nanobodies becomes fluorescent upon binding to their intracellular targets and enables background-free multicolor imaging and biosensing in living syst...

An estimated 10.8 million people worldwide were infected with tuberculosis (TB) in 2023, and among those cases, 1.25 million people succumbed to disease (1); 90% of people who become infected with Myc...

Here, the authors report metabolic activation as a potential antimicrobial strategy against Mycobacterium tuberculosis. They show that supra-physiological activation of L-histidine biosynthesis r...

Dual host-pathogen transcriptional profiling defines granuloma-specific programs during mycobacterial infection.

Brain imaging is illuminating the patterns linked to productive, positive dialogue, and those insights could help people connect with others

Using the visually accessible zebrafish-mycobacterium infection model, Wee et al demonstrate the caseous necrotic core of mycobacterial granulomas provides a safe-haven for opportunistic pathogens to ...

A new Harvard Chan School and BUSPH study projects that U.S. funding cuts to global health aid will have a catastrophic effect on pediatric TB.

Specialized macrophages are known to persist within tissue niches, but the molecular mechanisms guiding their sustained functional adaptation remain unclear. Kolter and Döring et al. show that local interactions between sensory nerves and macrophages activate TGF-β, which imprints and maintains nerve-associated macrophages that contribute to regeneration after tissue injury.

Safe gain-of-function research is necessary to identify new treatments for diseases like for tuberculosis — but the NIH has imposed unfounded stops.

YouTube video by Francis Crick Institute

Granulomas are classic manifestations of tuberculosis pathogenesis. They result from an ensemble of immune responses to Mycobacterium tuberculosis infection, but the identities, arrangement, cellular interactions, and regulation of the cells that comprise them have thus far been incompletely understood. To better understand the composition of granulomas, we conducted spatial and single-cell RNA sequencing of granulomas in biopsy specimens from patients with tuberculosis. We found that granulomas consist of concentric transcriptional laminae surrounding areas of central necrosis. We identified distinct populations of granuloma-associated stromal cells, fibroblasts, lymphocytes, mast cells, dendritic cells, neutrophils, and macrophages. Furthermore, gene expression among these cell populations differed by location within granulomas. We used inferential analysis to predict dominant granuloma cell-cell interactions, the activity of major signaling pathways, and transcription factor activities. Using spatial deconvolution, we mapped a conserved pattern of cellular organization dominated by macrophages rich in SPP1/osteopontin expression. Trajectory analysis of macrophage subtypes mapped their differentiation and supported the importance of SPP1 to granuloma macrophage polarization. Using the Mycobacterium marinum-zebrafish model, we found that mycobacterial infection induces spp1 expression in macrophages and that spp1 ablation results in granuloma formation defects and reduced survival in adult animals. Cumulatively, we have identified a dominant macrophage granuloma population as well as its central regulatory gene in human samples and confirmed the importance of spp1 to granuloma biology in vivo.

Tuberculosis is the world’s most deadly single-pathogen infection. Its causative bacterium, Mycobacterium tuberculosis, sickens over 10 million people annually. Mycobacterial granulomas are the pathol...

A review emphasizes the advantages of using zebrafish in research, outlines key differences in experimental approaches, and offers guidelines for designing studies in a way that enhances experimental ...

Researchers pinpoint the genes responsible for the final three pea traits studied by the famed citizen scientist.

MIT OpenCourseWare is a web based publication of virtually all MIT course content. OCW is open and available to the world and is a permanent MIT activity

The new administration wants “a break” from infectious disease research to focus on chronic disease. That’s impossible, writes Larry Schlesinger, an infectious disease doctor whose cancer was caused b...

Cases of the world’s deadliest infectious disease have been increasing in the U.S. in recent years

Kansas public health officials say the state's ongoing tuberculosis outbreak is the largest since the CDC started reporting TB cases in the 1950s.