Erratum: mycobacterium marinum infection of adult zebrafish causes caseating granulomatous tuberculosis and is moderated by adaptive immunity (Infection and Immunity (2006) 74, 11 (6108–6117))

Department of Microbiology, Box 357242, University of Washington, Seattle, WA 98195, USA.
Infection and Immunity (Impact Factor: 4.16). 12/2006; 74(11):6108-17. DOI: 10.1128/IAI.00887-06
Source: PubMed

ABSTRACT The zebrafish, a genetically tractable model vertebrate, is naturally susceptible to tuberculosis caused by Mycobacterium marinum, a close genetic relative of the causative agent of human tuberculosis, Mycobacterium tuberculosis. We previously developed a zebrafish embryo-M. marinum infection model to study host-pathogen interactions in the context of innate immunity. Here, we have constructed a flowthrough fish facility for the large-scale longitudinal study of M. marinum-induced tuberculosis in adult zebrafish where both innate and adaptive immunity are operant. We find that zebrafish are exquisitely susceptible to M. marinum strain M. Intraperitoneal injection of five organisms produces persistent granulomatous tuberculosis, while the injection of approximately 9,000 organisms leads to acute, fulminant disease. Bacterial burden, extent of disease, pathology, and host mortality progress in a time- and dose-dependent fashion. Zebrafish tuberculous granulomas undergo caseous necrosis, similar to human tuberculous granulomas. In contrast to mammalian tuberculous granulomas, zebrafish lesions contain few lymphocytes, calling into question the role of adaptive immunity in fish tuberculosis. However, like rag1 mutant mice infected with M. tuberculosis, we find that rag1 mutant zebrafish are hypersusceptible to M. marinum infection, demonstrating that the control of fish tuberculosis is dependent on adaptive immunity. We confirm the previous finding that M. marinum DeltaRD1 mutants are attenuated in adult zebrafish and extend this finding to show that DeltaRD1 predominantly produces nonnecrotizing, loose macrophage aggregates. This observation suggests that the macrophage aggregation defect associated with DeltaRD1 attenuation in zebrafish embryos is ongoing during adult infection.

Download full-text


Available from: Lynn Connolly, Aug 04, 2014
1 Follower
  • Source
    • "This study is, from our point of view, the most important evidence of how the zebrafish model can be used to validate and to re-postulate host–pathogen interactions during mycobacterial infection. On the other hand, Swaim et al. (2006) reported that lymphocytes play the same critical role in controlling mycobacterial infection in fishes and mammals by the use of a defective zebrafish mutant in the rag1 gene. They also demonstrated that bacteria defective in RD1 region are also attenuated in zebrafish. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Biological disease models can be difficult and costly to develop and use on a routine basis. Particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. When infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. Therefore, alternative and easy to handle models of experimental infections are still needed to test the virulence of bacterial lung pathogens. Because non-mammalian models have less ethical and cost constraints as a subjects for experimentation, in some cases would be appropriated to include these models as valuable tools to explore host-pathogen interactions. Numerous scientific data have been argued to the more extensive use of several kinds of alternative models, such as, the vertebrate zebrafish (Danio rerio), and non-vertebrate insects and nematodes (e.g., Caenorhabditis elegans) in the study of diverse infectious agents that affect humans. Here, we review the use of these vertebrate and non-vertebrate models in the study of bacterial agents, which are considered the principal causes of lung injury. Curiously none of these animals have a respiratory system as in air-breathing vertebrates, where respiration takes place in lungs. Despite this fact, with the present review we sought to provide elements in favor of the use of these alternative animal models of infection to reveal the molecular signatures of host-pathogen interactions.
    Frontiers in Microbiology 02/2015; 6:38. DOI:10.3389/fmicb.2015.00038 · 3.94 Impact Factor
  • Source
    • "At a molecular level, this coordinated macrophage death and re-phagocytosis is mediated through a specialized mycobacterial secretion system called ESX-1, most likely through its secreted effector ESAT6 (Davis and Ramakrishnan, 2009; Volkman et al., 2004; Volkman et al., 2010) (Figure 5). ESAT6 has been shown to induce apoptosis of infected cells in culture through multiple pathways, one or more of which may be operant in the granuloma (Choi et al., 2010; Derrick and Morris, 2007; Keane et al., 1997; Mishra et al., 2010; Swaim et al., 2006). ESX- 1/ESAT-6 also recruits macrophages by inducing host matrix metalloproteinase 9 (MMP9) in epithelial cells surrounding the nascent granuloma (Volkman et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Tuberculosis, an ancient disease of mankind, remains one of the major infectious causes of human death. We examine newly discovered facets of tuberculosis pathogenesis and explore the evolution of its causative organism Mycobacterium tuberculosis from soil dweller to human pathogen. M. tuberculosis has coevolved with the human host to evade and exploit host macrophages and other immune cells in multiple ways. Though the host can often clear infection, the organism can cause transmissible disease in enough individuals to sustain itself. Tuberculosis is a near-perfect paradigm of a host-pathogen relationship, and that may be the challenge to the development of new therapies for its eradication. Copyright © 2014 Elsevier Inc. All rights reserved.
    Cell 12/2014; 159(7). DOI:10.1016/j.cell.2014.11.024 · 33.12 Impact Factor
  • Source
    • "Such broad genetic analysis in laboratory models can then provide specific research models for diseases affecting both fish and humans. For example, forward genetic analyses in the zebrafish has uncovered essential mechanisms of tuberculosis infection and led to the identification of specific molecular regulators of resistance in fish (Swaim et al., 2006; Carvalho et al., 2011; Parikka et al., 2012; Ramakrishnan, 2013). Extension of these approaches can be applied to other infectious diseases (Sieger et al., 2009; Patterson et al., 2012) as well as how susceptibility is associated with the occurrence of other defects (e.g. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Fishes are wonderfully diverse. This variety is a result of the ability of ray-finned fishes to adapt to a wide range of environments, and has made them more specious than the rest of vertebrates combined. With such diversity it is easy to dismiss comparisons between distantly related fishes in efforts to understand the biology of a particular fish species. However, shared ancestry and the conservation of developmental mechanisms, morphological features and physiology provide the ability to use comparative analyses between different organisms to understand mechanisms of development and physiology. The use of species that are amenable to experimental investigation provides tools to approach questions that would not be feasible in other ‘non-model’ organisms. For example, the use of small teleost fishes such as zebrafish and medaka has been powerful for analysis of gene function and mechanisms of disease in humans, including skeletal diseases. However, use of these fish to aid in understanding variation and disease in other fishes has been largely unexplored. This is especially evident in aquaculture research. Here we highlight the utility of these small laboratory fishes to study genetic and developmental factors that underlie skeletal malformations that occur under farming conditions. We highlight several areas in which model species can serve as a resource for identifying the causes of variation in economically important fish species as well as to assess strategies to alleviate the expression of the variant phenotypes in farmed fish. We focus on genetic causes of skeletal deformities in the zebrafish and medaka that closely resemble phenotypes observed both in farmed as well as natural populations of fishes.
    Journal of Applied Ichthyology 08/2014; 30(4). DOI:10.1111/jai.12533 · 0.90 Impact Factor