title: Real-time visualization of mycobacterium-macrophage interactions leading to initiation of granuloma formation in zebrafish embryos.
abstract: Infection of vertebrate hosts with pathogenic Mycobacteria, the agents of tuberculosis, produces granulomas, highly organized structures containing differentiated macrophages and lymphocytes, that sequester the pathogen. Adult zebrafish are naturally susceptible to tuberculosis caused by Mycobacterium marinum. Here, we exploit the optical transparency of zebrafish embryos to image the events of M. marinum infection in vivo. Despite the fact that the embryos do not yet have lymphocytes, infection leads to the formation of macrophage aggregates with pathological hallmarks of granulomas and activation of previously identified granuloma-specific Mycobacterium genes. Thus, Mycobacterium-macrophage interactions can initiate granuloma formation solely in the context of innate immunity. Strikingly, infection can redirect normal embryonic macrophage migration, even recruiting macrophages seemingly committed to their developmentally dictated tissue sites.
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors.forename: J Muse
authors.initials: JM
authors.lastname: Davis
authors.forename: Hilary
authors.initials: H
authors.lastname: Clay
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Lewis
authors.forename: Nafisa
authors.initials: N
authors.lastname: Ghori
authors.forename: Philippe
authors.initials: P
authors.lastname: Herbomel
authors.forename: Lalita
authors.initials: L
authors.lastname: Ramakrishnan
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000276:immunology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D006099:Granuloma / Q000276:immunology* / Q000382:microbiology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D018715:Microscopy, Video; D019910:Mycobacterium marinum / Q000502:physiology* / Q000648:ultrastructure; D015027:Zebrafish / Q000196:embryology / Q000276:immunology* / Q000382:microbiology