Fit for consumption: zebrafish as a model for tuberculosis

Cronan, Mark R.; Tobin, David M.

doi:10.1242/dmm.016089

Cited by 101 publications

(87 citation statements)

References 92 publications

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“…Zebrafish excel as a model to uncover gene function (59,60) and are now advancing research in many fields, including stem cell biology (61,62), cancer (63,64), infectious disease (65,66), and autoimmune disease studies (67,68). In this context, we consider the identification of expressed genes in our zebrafish MHC assembly to be noteworthy.…”

Section: Discussionmentioning

confidence: 99%

Alternative haplotypes of antigen processing genes in zebrafish diverged early in vertebrate evolution

McConnell

Hernandez

Wcisel

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Antigen processing and presentation genes found within the MHC are among the most highly polymorphic genes of vertebrate genomes, providing populations with diverse immune responses to a wide array of pathogens. Here, we describe transcriptome, exome, and whole-genome sequencing of clonal zebrafish, uncovering the most extensive diversity within the antigen processing and presentation genes of any species yet examined. Our CG2 clonal zebrafish assembly provides genomic context within a remarkably divergent haplotype of the core MHC region on chromosome 19 for six expressed genes not found in the zebrafish reference genome: mhc1uga, proteasome-β 9b (psmb9b), psmb8f, and previously unknown genes psmb13b, tap2d, and tap2e. We identify ancient lineages for Psmb13 within a proteasome branch previously thought to be monomorphic and provide evidence of substantial lineage diversity within each of three major trifurcations of catalytic-type proteasome subunits in vertebrates: Psmb5/Psmb8/Psmb11, Psmb6/ Psmb9/Psmb12, and Psmb7/Psmb10/Psmb13. Strikingly, nearby tap2 and MHC class I genes also retain ancient sequence lineages, indicating that alternative lineages may have been preserved throughout the entire MHC pathway since early diversification of the adaptive immune system ∼500 Mya. Furthermore, polymorphisms within the three MHC pathway steps (antigen cleavage, transport, and presentation) are each predicted to alter peptide specificity. Lastly, comparative analysis shows that antigen processing gene diversity is far more extensive than previously realized (with ancient coelacanth psmb8 lineages, shark psmb13, and tap2t and psmb10 outside the teleost MHC), implying distinct immune functions and conserved roles in shaping MHC pathway evolution throughout vertebrates.comparative genomics | proteasome and TAP evolution | major histocompatibility | MHC class I pathway | CG2 clonal zebrafish

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Section: Discussionmentioning

confidence: 99%

Alternative haplotypes of antigen processing genes in zebrafish diverged early in vertebrate evolution

McConnell

Hernandez

Wcisel

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Finally, it is important to mention that zebrafish model has also been shown to be very useful to elucidate the early events of the mycobacterial infection, particularly in the study of the mechanisms of granuloma formation and its role in controlling the infection [5]. Infection of zebrafish with M. marinum, a closest relative of MTBC, resembles many aspects of human tuberculosis; in fact, crucial virulence factors, host genes and immune cell types are conserved in the zebrafish-M. marinum model [7]. Using this model, the bacterial RD1 locus was found to be required for efficient granuloma formation and that the ESX-1 system was responsible for the cell death of infected macrophages [8].…”

Section: Models For Measuring Mtb Virulencementioning

confidence: 99%

Virulence Factors and Pathogenicity of Mycobacterium

Echeverría-Valencia¹,

Flores-Villalva²,

Espitia³

2018

Mycobacterium - Research and Development

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Virulence, is referred as the ability of a pathogen to cause disease, and for mycobacteria it depends on their ability to reside within host cells and evade the microbicidal mechanisms of macrophages. The outcome of tuberculosis (TB) infection is highly variable and it seems that the closest relationship between the Mycobacterium genre and humans has shaped the mycobacterial genome to encode bacterial factors that reflects a highly evolved and coordinated program of immune evasion strategies that interfere with both innate and adaptive immunity causing disease even in fully immunocompetent host. Although Mycobacterium tuberculosis (MTB) does not have classical virulence factors, it has described many virulence-associated genes and virulence lifestyle genes from Mycobacterium tuberculosis complex (MTBC). In this chapter, we describe the most important gene/molecule involved in the host defense modulation response, also the plethora of strategies to evade immune mechanisms of macrophage. We review the main genes whose inactivation in the mycobacterial genome leads to a measurable loss in virulence in the different validated TB models.

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“…Necrosis and then hypoxia result in caseum formation in the granuloma's inner core. Bacteria persist inside this granuloma and eventually are released when this granuloma ruptures [23]. Mtb binds to receptors on macrophages, including Toll-like receptors, Nod-like receptors, C-type lectin receptors, mannose receptor, DC-SIGN (dendritic cell-specific intracellular adhesion molecule 3-grabbing nonintegrin), complement receptors, Fc receptors, and DNA sensors.…”

Section: Pathogenesismentioning

confidence: 99%

“…Although the immune response in the lung is directed at eliminating the bacillus, activation of pathways that damage lung tissue results in fibrosis, scar formation, and impaired lung function. Hence, mycobacterial phagocytosis is not exclusively host driven; instead, it is a process tuned by the mycobacteria themselves to establish a productive niche for their growth and dissemination [23].…”

Section: Pathogenesismentioning

confidence: 99%

“…In addition, multiple secretion systems were identified (ESX-1 system, which ESAT-6 is part of, and SecA2 system) and found to facilitate granuloma formation and lead to macrophage death and recruitment of more macrophages. ESAT-6 induces the inflammatory matrix metalloprotease, MMP-9, in adjacent epithelial cells, acting as a guidance cue for nearby macrophages, leading to further bacterial expansion and granuloma formation [23].…”

Section: Pathogenesismentioning

confidence: 99%

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