ArticleDisease models & mechanisms2015
CLARITY and PACT-based imaging of adult zebrafish and mouse for whole-animal analysis of infections.
Article in Disease models & mechanisms, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 60 citations in OpenAlex.
- Imaging cellular activity simultaneously across all organs of a vertebrate reveals body-wide circuits.bioRxiv : the preprint server for biology · 2025Article
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- Correlative 3D imaging method for analysing lesion architecture in susceptible mice infected with Mycobacterium tuberculosis.Disease models & mechanisms · 2025Article
- Building Spatiotemporal Understanding ofACS infectious diseases · 2025Review
- Deep learning-based adaptive optics for light sheet fluorescence microscopy.Biomedical optics express · 2023Article
- TSA-PACT: a method for tissue clearing and immunofluorescence staining on zebrafish brain with improved sensitivity, specificity and stability.Cell & bioscience · 2023Article
- Evidence for RNA or protein transport from somatic tissues to the male reproductive tract in mouse.eLife · 2023Article
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- Quantitative analysis of illumination and detection corrections in adaptive light sheet fluorescence microscopy.Biomedical optics express · 2022Article
- Spatial relationships of intra-lesion heterogeneity in Mycobacterium tuberculosis microenvironment, replication status, and drug efficacy.PLoS pathogens · 2022Article
- Imaging Infection Across Scales of Size: From Whole Animals to Single Molecules.Annual review of microbiology · 2021Review
- Imaging the Gut with "CLARITY".Journal of visualized experiments : JoVE · 2021Article
- Article
- Complementary and divergent functions of zebrafish Tango1 and Ctage5 in tissue development and homeostasis.Molecular biology of the cell · 2021Article
- New Look at RSV Infection: Tissue Clearing and 3D Imaging of the Entire Mouse Lung at Cellular Resolution.Viruses · 2021Article
- Exploiting Fluorescent Proteins to Understand Mycobacterium tuberculosis Biology.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Three-dimensional in situ morphometrics of Mycobacterium tuberculosis infection within lesions by optical mesoscopy and novel acid-fast staining.Scientific reports · 2020Article
- Biomedical Applications of Tissue Clearing and Three-Dimensional Imaging in Health and Disease.iScience · 2020Review
- 3D Imaging of the TransparentFrontiers in cellular and infection microbiology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Visualization of infection and the associated host response has been challenging in adult vertebrates. Owing to their transparency, zebrafish larvae have been used to directly observe infection in vivo; however, such larvae have not yet developed a functional adaptive immune system. Cells involved in adaptive immunity mature later and have therefore been difficult to access optically in intact animals. Thus, the study of many aspects of vertebrate infection requires dissection of adult organs or ex vivo isolation of immune cells. Recently, CLARITY and PACT (passive clarity technique) methodologies have enabled clearing and direct visualization of dissected organs. Here, we show that these techniques can be applied to image host-pathogen interactions directly in whole animals. CLARITY and PACT-based clearing of whole adult zebrafish and Mycobacterium tuberculosis-infected mouse lungs enables imaging of mycobacterial granulomas deep within tissue to a depth of more than 1 mm. Using established transgenic lines, we were able to image normal and pathogenic structures and their surrounding host context at high resolution. We identified the three-dimensional organization of granuloma-associated angiogenesis, an important feature of mycobacterial infection, and characterized the induction of the cytokine tumor necrosis factor (TNF) within the granuloma using an established fluorescent reporter line. We observed heterogeneity in TNF induction within granuloma macrophages, consistent with an evolving view of the tuberculous granuloma as a non-uniform, heterogeneous structure. Broad application of this technique will enable new understanding of host-pathogen interactions in situ.
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