Animal models in tuberculosis research – where is the beef?

Myllymäki, Henna; Niskanen, Mirja; Oksanen, Kaisa; Rämet, Mika

doi:10.1517/17460441.2015.1049529

Cited by 38 publications

(46 citation statements)

References 110 publications

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“…On the other hand, in animal models it is possible to study all the stages of the TB infection, although their ability to replicate the different aspects of human TB pathology varies. The major models used are mice, guinea pigs and rabbits [5]. Mice is the most frequent in vivo model used because of their well-characterized genetics and the huge collection of immunological reagents as well as the existence of inbred strains, their susceptibility to MTB is low and their pathology is unlike that in humans [5].…”

Section: Models For Measuring Mtb Virulencementioning

confidence: 99%

“…The major models used are mice, guinea pigs and rabbits [5]. Mice is the most frequent in vivo model used because of their well-characterized genetics and the huge collection of immunological reagents as well as the existence of inbred strains, their susceptibility to MTB is low and their pathology is unlike that in humans [5]. Guinea pigs are very sensitive to MTB and develop a disease with multiple similarities to human disease, such as lung necrosis, lymphadenopathy and disease dissemination.…”

Section: Models For Measuring Mtb Virulencementioning

confidence: 99%

“…The most important parameters associated with virulence in animal models, besides mortality and morbidity, are: the bacterial load, the numbers of bacteria found in the infected host after the initial infection, histopathological changes and inflammatory responses. 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].…”

Section: Models For Measuring Mtb Virulencementioning

confidence: 99%

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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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Section: Models For Measuring Mtb Virulencementioning

confidence: 99%

Section: Models For Measuring Mtb Virulencementioning

confidence: 99%

Section: Models For Measuring Mtb Virulencementioning

confidence: 99%

See 1 more Smart Citation

Virulence Factors and Pathogenicity of Mycobacterium

Echeverría-Valencia¹,

Flores-Villalva²,

Espitia³

2018

Mycobacterium - Research and Development

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“…Each model mimics one or more features of human TB, including clinical signs, pathological changes, bacteria loads in organs, disease progressions or immunological parameters (Rodgers et al, 2007; Waters et al, 2011; Clark et al, 2015; Myllymaki et al, 2015; Peng et al, 2015; Provan and Newland, 2015; Kramnik and Beamer, 2016; Phuah et al, 2016). Characteristics, as well as pros and cons, of current TB animal models are summarized, the utility of each model according to the pros and cons was also speculated.…”

Section: Current Use Of Tb Animal Modelsmentioning

confidence: 99%

“…The latency length and relapse level of TB show great variation within group, and the latent-relapse period very long (Myllymaki et al, 2015)…”

Section: Current Use Of Tb Animal Modelsmentioning

confidence: 99%

Animal Models for Tuberculosis in Translational and Precision Medicine

Tang

Sun

et al. 2017

Front. Microbiol.

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Tuberculosis (TB) is a health threat to the global population. Anti-TB drugs and vaccines are key approaches for TB prevention and control. TB animal models are basic tools for developing biomarkers of diagnosis, drugs for therapy, vaccines for prevention and researching pathogenic mechanisms for identification of targets; thus, they serve as the cornerstone of comparative medicine, translational medicine, and precision medicine. In this review, we discuss the current use of TB animal models and their problems, as well as offering perspectives on the future of these models.

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Colony-stimulating factor-1- and interleukin-34-derived macrophages differ in their susceptibility to Mycobacterium marinum

Popović

Yaparla

Paquin‐Proulx

et al. 2019

Journal of Leukocyte Biology

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Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains the leading global cause of death from an infectious agent. Mycobacteria thrive within their host M s and presently, there is no animal model that permits combined in vitro and in vivo study of mycobacteria-host M interactions. Mycobacterium marinum (Mm), which causes TB in aquatic vertebrates, has become a promising model for TB research, owing to its close genetic relatedness to Mtb and the availability of alternative, natural host aquatic animal models. Here, we adopted the Xenopus laevis frog-Mm surrogate infection model to study host M susceptibility and resistance to mycobacteria. M differentiation is regulated though the CSF-1 receptor (CSF-1R), which is activated by CSF-1 and the unrelated IL-34 cytokines. Using combined in vitro and in vivo approaches, we demonstrated that CSF-1-M s exacerbate Mm infections, are more susceptible to mycobacterial entry and are less effective at killing this pathogen. By contrast, IL-34-M s confer anti-Mm resistance in vivo, are less susceptible to Mm entry and more effectively eliminate internalized mycobacteria. Moreover, we showed that the human CSF-1-and IL-34-M s are likewise, respectively, susceptible and resistant to mycobacteria, and that both frog and human CSF-1-M s are more prone to the spread of mycobacteria and to being infected by Mm-laden M s than the respective IL-34-M subsets. This work marks the first report describing the roles of these M subsets in mycobacterial disease and may well lead to the development of more targeted anti-Mtb approaches.

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Animal models in tuberculosis research – where is the beef?

Cited by 38 publications

References 110 publications

Virulence Factors and Pathogenicity of Mycobacterium

Virulence Factors and Pathogenicity of Mycobacterium

Animal Models for Tuberculosis in Translational and Precision Medicine

Colony-stimulating factor-1- and interleukin-34-derived macrophages differ in their susceptibility to Mycobacterium marinum

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