Monkey Models of Tuberculosis: Lessons Learned

Peña, Juliet C.; Ho, Wen‐Zhe

doi:10.1128/iai.02850-14

Cited by 80 publications

(72 citation statements)

References 65 publications

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“…In the skeleton, this inability to restrict mycobacterial growth would have led to a rapid formation of granulomatous lesions and bone destruction. A similar situation is observable in non-human primates, for whom susceptibility to TB is generally higher than in humans, the acute form is prevalent (Peña and Ho, 2015), and survival time is…”

Section: Rationale Of the Studymentioning

confidence: 79%

Insights on the paleoepidemiology of ancient tuberculosis from the structural analysis of postcranial remains from the Ligurian Neolithic (northwestern Italy)

Sparacello

Roberts

Canci

et al. 2016

International Journal of Paleopathology

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Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. Abstract: The aim of this research was to gain insights on the timeline of progression of osteoarticular tuberculosis (TB) in people from the Neolithic period by using skeletal traits that are independent of the bony lesions. The body proportions and postcranial mechanical strength of bones from two individuals from Liguria in northwestern Italy (Arene Candide 5, adolescent, and Arma dell'Aquila 1, adult), were compared with the rest of the Ligurian Neolithic skeletal series (45 individuals). If TB led to wasting of the skeleton and lack of normal function which endured for years, as often happens today, a clear signature of postcranial gracility and disruption of development should be apparent. Conversely, rapid progress of the disease would leave little systemic macroscopic change in the skeleton, except for the bony lesions directly caused by the TB pathogen, suggesting a different level of bacterial virulence in the past. The extreme biomechanical gracility observed in the lower limb of Arene Candide 5 suggests a period of compromised diaphyseal periosteal apposition during ontogeny due to metabolic disturbances likely linked to TB. Results suggest that, in Neolithic Liguria, TB in humans saw a slow, chronic progression, which is characteristic of diseases with long histories of host-pathogen coevolution. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64

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Section: Rationale Of the Studymentioning

confidence: 79%

Insights on the paleoepidemiology of ancient tuberculosis from the structural analysis of postcranial remains from the Ligurian Neolithic (northwestern Italy)

Sparacello

Roberts

Canci

et al. 2016

International Journal of Paleopathology

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“…Several animal models have been used throughout the past few decades to study TB, including zebrafish 120 , mice 121 and non-human primates 122–124 . Each system has both benefits and limitations as a model of TB, and although none perfectly recapitulates human M. tuberculosis infection, they all contribute to our understanding of this disease.…”

Section: Figure 1 |mentioning

confidence: 99%

Heterogeneity in tuberculosis

2017

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Infection with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), results in a range of clinical presentations in humans. Most infections manifest as a clinically asymptomatic, contained state that is termed latent TB infection (LTBI); a smaller subset of infected individuals present with symptomatic, active TB. Within these two seemingly binary states, there is a spectrum of host outcomes that have varying symptoms, microbiologies, immune responses and pathologies. Recently, it has become apparent that there is diversity of infection even within a single individual. A good understanding of the heterogeneity that is intrinsic to TB — at both the population level and the individual level — is crucial to inform the development of intervention strategies that account for and target the unique, complex and independent nature of the local host–pathogen interactions that occur in this infection. In this Review, we draw on model systems and human data to discuss multiple facets of TB biology and their relationship to the overall heterogeneity observed in the human disease.

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“…The animal models most closely resembling human M. tuberculosis infection are non-human primates e.g. the macaque [9,10]. However ethical, cost, and practical considerations limit widespread use [6].…”

Section: Introductionmentioning

confidence: 99%

Galleria mellonella - a novel infection model for the Mycobacterium tuberculosis complex

Spiropoulos

Cooley

et al. 2018

Virulence

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Animal models have long been used in tuberculosis research to understand disease pathogenesis and to evaluate novel vaccine candidates and anti-mycobacterial drugs. However, all have limitations and there is no single animal model which mimics all the aspects of mycobacterial pathogenesis seen in humans. Importantly mice, the most commonly used model, do not normally form granulomas, the hallmark of tuberculosis infection. Thus there is an urgent need for the development of new alternative in vivo models. The insect larvae, Galleria mellonella has been increasingly used as a successful, simple, widely available and cost-effective model to study microbial infections. Here we report for the first time that G. mellonella can be used as an infection model for members of the Mycobacterium tuberculosis complex. We demonstrate a dose-response for G. mellonella survival infected with different inocula of bioluminescent Mycobacterium bovis BCG lux, and demonstrate suppression of mycobacterial luminesence over 14 days. Histopathology staining and transmission electron microscopy of infected G. mellonella phagocytic haemocytes show internalization and aggregation of M. bovis BCG lux in granuloma-like structures, and increasing accumulation of lipid bodies within M. bovis BCG lux over time, characteristic of latent tuberculosis infection. Our results demonstrate that G. mellonella can act as a surrogate host to study the pathogenesis of mycobacterial infection and shed light on host-mycobacteria interactions, including latent tuberculosis infection.

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Monkey Models of Tuberculosis: Lessons Learned

Cited by 80 publications

References 65 publications

Insights on the paleoepidemiology of ancient tuberculosis from the structural analysis of postcranial remains from the Ligurian Neolithic (northwestern Italy)

Insights on the paleoepidemiology of ancient tuberculosis from the structural analysis of postcranial remains from the Ligurian Neolithic (northwestern Italy)

Heterogeneity in tuberculosis

Galleria mellonella - a novel infection model for the Mycobacterium tuberculosis complex

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