Mycobacterium marinum infection drives foam cell differentiation in zebrafish infection models

Johansen, Matt D.; Kasparian, Joshua A.; Hortle, Elinor; Britton, Warwick J.; Purdie, Auriol C.; Oehlers, Stefan H.

doi:10.1016/j.dci.2018.07.022

Cited by 31 publications

(31 citation statements)

References 10 publications

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“…Macrophage reprogramming that parallel E-cadherin-dependent mesenchymal-epithelial transitions contribute to organized granuloma formation (Cronan et al, 2016). Foam-like cells have also been identified using the zebrafish-M. marinum granuloma model, where transdifferentiation of macrophages appears driven by the mycobacterial ESX1 pathogenicity locus (Johansen et al, 2018). Vascularization further supports granuloma formation, driven in part through CXCR4 (Torraca et al, 2017), angiopoietin-2 (Oehlers et al, 2017), and VEGF (Walton et al, 2018).…”

Section: Granulomasmentioning

confidence: 99%

Teleost contributions to the understanding of mycobacterial diseases

Hodgkinson

Belosevic

Elks

et al. 2019

Developmental & Comparative Immunology

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Few pathogens have shaped human medicine as the mycobacteria. From understanding biological phenomena driving disease spread, to mechanisms of hostpathogen interactions and antibiotic resistance, the Mycobacterium genus continues to challenge and offer insights into the basis of health and disease. Teleost fish models of mycobacterial infections have progressed significantly over the past three decades, now supplying a range of unique tools and new opportunities to define the strategies employed by these Gram-positive bacteria to overcome host defenses, as well as those host antimicrobial pathways that can be used to limit its growth and spread. Herein, we take a comparative perspective and provide an update on the contributions of teleost models to our understanding of mycobacterial diseases.

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Section: Granulomasmentioning

confidence: 99%

Teleost contributions to the understanding of mycobacterial diseases

Hodgkinson

Belosevic

Elks

et al. 2019

Developmental & Comparative Immunology

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“…This section continues from step 5.9. Oil Red O staining for foam cells (protocol for isopropanol solvent is similar just substitute isopropanol of propylene glycol in steps c, d, e) (Johansen et al, 2018). Postfix slides in fixative for 5-10 minutes at room temperature. Filter 0.5% (w/v) Oil Red O (Sigma-Aldrich O0625) dissolved in propylene glycol to remove precipitate. Rinse slides twice in PBS for 5 minutes to remove fixative. Rinse slides twice in propylene glycol for 5 minutes. Stain slides in 0.5% (w/v) Oil Red O propylene glycol solution for 15 minutes. Rinse slides twice in propylene glycol for 5 minutes to remove background staining. Rinse slides briefly in PBS. Counterstain slides with a 1% (w/v) solution of methylene blue (Sigma-Aldrich M9140) dissolved in water or hematoxylin for 1 minute. Rinse slides briefly in tap water. Add 2-3 drops of with aqueous mounting media (Clear-Mount, Proscitech IM032) and mount coverslip. Image by light microscopy. Picrosirius red staining for extracellular matrix remodeling.…”

Section: Non-fluorescence Correlative Staining and Microscopymentioning

confidence: 99%

High content analysis of granuloma histology and neutrophilic inflammation in adult zebrafish infected with Mycobacterium marinum

Cheng

Kam

Johansen

et al. 2019

Preprint

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Infection of zebrafish with natural pathogen Mycobacterium marinum is a useful surrogate for studying the human granulomatous inflammatory response to infection by Mycobacterium tuberculosis. The adaptive immune system of the adult stage zebrafish offers an advance on the commonly used embryo infection model as adult zebrafish form granulomas with striking similarities to human-M. tuberculosis granulomas. Here, we present workflows to perform high content analyses of granulomas in adult zebrafish infected with M. marinum by cryosectioning to take advantage of strong endogenous transgenic fluorescence adapted from common zebrafish embryo infection tools. Specific guides to classifying granuloma necrosis and organisation, quantifying bacterial burden and leukocyte infiltration of granulomas, and visualizing extracellular matrix remodelling and foam cell formation are also provided. We use these methods to characterize neutrophil recruitment to M. marinum granulomas across time and find an inverse relation to granuloma necrosis suggesting granuloma necrosis is not a marker of immunopathology in the natural infection system of the adult zebrafish-M. marinum pairing. The methods can be easily translated to studying the zebrafish adaptive immune response to other chronic and granuloma-forming pathogens.

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“…Oil Red O lipid staining on whole mount embryos was completed as previously described (Johansen et al, 2018b;Passeri et al, 2009). Briefly, embryos were individually imaged for bacterial distribution by fluorescent microscopy, fixed, and stained in Oil Red O (0.5% w/v in propylene glycol).…”

Section: Oil Red O Stainingmentioning

confidence: 99%

“…M. marinum is a natural pathogen of fish and amphibian species and genomic analysis has identified M. marinum as the closest genetic relative of the Mtb complex, sharing 85% of orthologous regions with Mtb (Stinear et al, 2008). Zebrafish models of M. marinum infection have provided unique insight into host-pathogen interplay responsible for granuloma formation, exquisitely reproducing the cellular structure of the human-M. tuberculosis granulomas, including the presence of lipid-rich foam cells (Cronan et al, 2016;Johansen et al, 2018b;Oehlers et al, 2017;Oehlers et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Analysis of mycobacterial infection-induced changes to host lipid metabolism in a zebrafish infection model reveals a conserved role for LDLR in infection susceptibility

Johansen

Hortle

Kasparian

et al. 2018

Fish & Shellfish Immunology

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Changes to lipid metabolism are well-characterised consequences of human tuberculosis infection but their functional relevance are not clearly elucidated in these or other host-mycobacterial systems. The zebrafish-Mycobacterium marinum infection model is used extensively to model many aspects of human-M. tuberculosis pathogenesis but has not been widely used to study the role of infection-induced lipid metabolism. We find mammalian mycobacterial infection-induced alterations in host Low Density Lipoprotein metabolism are conserved in the zebrafish model of mycobacterial pathogenesis. Depletion of LDLR, a key lipid metabolism node, decreased M. marinum burden, and corrected infection-induced altered lipid metabolism resulting in decreased LDL and reduced the rate of macrophage transformation into foam cells. Our results demonstrate a conserved role for infection-induced alterations to host lipid metabolism, and specifically the LDL-LDLR axis, across host-mycobacterial species pairings.

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Mycobacterium marinum infection drives foam cell differentiation in zebrafish infection models

Cited by 31 publications

References 10 publications

Teleost contributions to the understanding of mycobacterial diseases

Teleost contributions to the understanding of mycobacterial diseases

High content analysis of granuloma histology and neutrophilic inflammation in adult zebrafish infected with Mycobacterium marinum

Analysis of mycobacterial infection-induced changes to host lipid metabolism in a zebrafish infection model reveals a conserved role for LDLR in infection susceptibility

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