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, Matt D.; Hortle, Elinor; Kasparian, Joshua A.; Romero, Alejandro; Novoa, Beatriz; Figueras, António; Britton, Warwick J.; Silva, Kumudika de; Purdie, Auriol C.; Oehlers, Stefan H.

doi:10.1016/j.fsi.2018.09.037

Cited by 8 publications

(3 citation statements)

References 18 publications

(21 reference statements)

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“…ESAT-6 has been shown to play a role in the infection of M. tuberculosis [ 94 ], as well as in the escape from phagosomes. ESX-1 has also been shown to play a role in inducing the differentiation of macrophages into foam cells [ 100 ], which is necessary for the acquisition of LDLR by the bacterium. While not all members of the genus Mycobacterium possess a ESX-1 secretion system, it has recently been reported that ESX-4 could play a similar role in the regulation of intracellular growth and phagosomal escape [ 101 ].…”

Section: Virulence Factorsmentioning

confidence: 99%

Mycobacteriosis and Infections with Non-tuberculous Mycobacteria in Aquatic Organisms: A Review

2020

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The Mycobacteriaceae constitute a family of varied Gram-positive organisms that include a large number of pathogenic bacteria. Among these, non-tuberculous mycobacteria are endemic worldwide and have been associated with infections in a large number of organisms, including humans and other mammals and reptiles, as well as fish. In this review, we summarize the most recent findings regarding this group of pathogens in fish. There, four species are most commonly associated with disease outbreaks: Mycobacterium marinum, the most common of these fish mycobacterial pathogens, Mycobacterium fortuitum, Mycobacterium gordonae, and Mycobacterium chelonae. These bacteria have a broad host range: they are zoonotic, and infections have been reported in a large number of fish species. The main route of entry of the bacterium into the fish is through the gastrointestinal route, and the disease is associated with ulcerative dermatitis as well as organomegaly and the development of granulomatous lesions in the internal organs. Mycobacteriaceae are slow-growing and fastidious and isolation is difficult and time consuming and diagnostic is mostly performed using serological and molecular tools. Control of the disease is also difficult: there is currently no effective vaccine and infections react poorly to antibiotherapy. For this reason, more research is needed on the subject of these vexing pathogens.

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Section: Virulence Factorsmentioning

confidence: 99%

Mycobacteriosis and Infections with Non-tuberculous Mycobacteria in Aquatic Organisms: A Review

2020

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“…HSP72 and LDLR were the most targeted genes by the H37Rv-specific miRNAs. These genes are involved in the interaction between neutrophils and macrophages during the early phase of the innate immune response to Mtb infection (52) as well as in the control of infectious load and infection-induced changes in lipid metabolism (53), respectively.…”

Section: Discussionmentioning

confidence: 99%

Integrative Analysis of Human Macrophage Inflammatory Response Related to Mycobacterium tuberculosis Virulence

et al. 2021

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Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, kills 1.5 to 1.7 million people every year. Macrophages are Mtb’s main host cells and their inflammatory response is an essential component of the host defense against Mtb. However, Mtb is able to circumvent the macrophages’ defenses by triggering an inappropriate inflammatory response. The ability of Mtb to hinder phagolysosome maturation and acidification, and to escape the phagosome into the cytosol, is closely linked to its virulence. The modulation of the host inflammatory response relies on Mtb virulence factors, but remains poorly studied. Understanding macrophage interactions with Mtb is crucial to develop strategies to control tuberculosis. The present study aims to determine the inflammatory response transcriptome and miRNome of human macrophages infected with the virulent H37Rv Mtb strain, to identify macrophage genetic networks specifically modulated by Mtb virulence. Using human macrophages infected with two different live strains of mycobacteria (live or heat-inactivated Mtb H37Rv and M. marinum), we quantified and analyzed 184 inflammatory mRNAs and 765 micro(mi)RNAs. Transcripts and miRNAs differently modulated by H37Rv in comparison with the two other conditions were analyzed using in silico approaches. We identified 30 host inflammatory response genes and 37 miRNAs specific for H37Rv virulence, and highlight evidence suggesting that Mtb intracellular-linked virulence depends on the inhibition of IL-1β-dependent pro-inflammatory response, the repression of apoptosis and the delay of the recruitment and activation of adaptive immune cells. Our findings provide new potential targets for the development of macrophage-based therapeutic strategies against TB.

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“…Infections were studied through the natural route using bath exposures and it was observed that the gastrointestinal track was the primary route of infection [102]. The M. marinum infection-induced lipid metabolism was furthermore studied using the zebrafish model [112,113].…”

Section: Bacteriamentioning

confidence: 99%

Zebrafish as a Model for Fish Diseases in Aquaculture

Jørgensen

2020

Pathogens

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The use of zebrafish as a model for human conditions is widely recognized. Within the last couple of decades, the zebrafish has furthermore increasingly been utilized as a model for diseases in aquacultured fish species. The unique tools available in zebrafish present advantages compared to other animal models and unprecedented in vivo imaging and the use of transgenic zebrafish lines have contributed with novel knowledge to this field. In this review, investigations conducted in zebrafish on economically important diseases in aquacultured fish species are included. Studies are summarized on bacterial, viral and parasitic diseases and described in relation to prophylactic approaches, immunology and infection biology. Considerable attention has been assigned to innate and adaptive immunological responses. Finally, advantages and drawbacks of using the zebrafish as a model for aquacultured fish species are discussed.

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

Cited by 8 publications

References 18 publications

Mycobacteriosis and Infections with Non-tuberculous Mycobacteria in Aquatic Organisms: A Review

Mycobacteriosis and Infections with Non-tuberculous Mycobacteria in Aquatic Organisms: A Review

Integrative Analysis of Human Macrophage Inflammatory Response Related to Mycobacterium tuberculosis Virulence

Zebrafish as a Model for Fish Diseases in Aquaculture

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