Evidence for a rhesus monkey model of asymptomatic tuberculosis

Gormus, Bobby J.; Blanchard, James; Alvarez, X.; Didier, Peter J.

doi:10.1111/j.1600-0684.2004.00062.x

Cited by 60 publications

(65 citation statements)

References 39 publications

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“…The early investigations during the Golden Age (17-21) specifically showed that M. tuberculosis infection in RM progresses rapidly, within 8 to 9 weeks after aerosol inhalation of the H37Rv strain administered at low doses of up to 62 CFU. In 2004, the Tulane NPRC established a model of asymptomatic, or latent, M. tuberculosis infection of RM (26). The investigators there revealed that RM are a good model for not only active TB but also asymptomatic TB when the investigators used lower doses (30 CFU) of the H37Rv strain.…”

Section: Rhesus Macaquesmentioning

confidence: 99%

“…A series of subsequent investigations were dedicated to macaque research to assess novel TB vaccines and drugs, as well as to gain an understanding of the pathogenesis of M. tuberculosis infection and reactivation. Figures 2 and 3 abridge the RM (13,(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43) and CM (10,15,25,(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59) models of experimental M. tuberculosis infection after the Golden Age, from 2001 to 2014.…”

Section: Historical Outlook On Macaque Modelsmentioning

confidence: 99%

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Monkey Models of Tuberculosis: Lessons Learned

Peña

2015

Infect Immun

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bThe use of animal models has been invaluable for studying the pathogenesis of Mycobacterium tuberculosis infection, as well as for testing the efficacy of vaccines and drug regimens for tuberculosis. Among the applied animal models, nonhuman primates, particularly macaques, share the greatest anatomical and physiological similarities with humans. As such, macaque models have been used for investigating tuberculosis pathogenesis and preclinical testing of drugs and vaccines. This review focuses on published major studies which illustrate how the rhesus and cynomolgus macaques have enriched and may continue to advance the field of global tuberculosis research.

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Section: Rhesus Macaquesmentioning

confidence: 99%

Section: Historical Outlook On Macaque Modelsmentioning

confidence: 99%

Monkey Models of Tuberculosis: Lessons Learned

Peña

2015

Infect Immun

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“…The Erdman strain has also been used in rhesus and cynomolgus macaques by other research groups (17)(18)(19)(20)(21), and a comparison of BCG vaccination followed by high-dose M. tuberculosis strain Erdman challenge in these two species suggested that cynomolgus macaques had improved control of infection (22). There is evidence for LTBI in rhesus macaques using the H37Rv strain delivered at a low dose (23) or the less virulent strain CDC1551 strain delivered at higher doses and reactivation of CDC1551 LTBI by SIV (24). The route of challenge (aerosol versus bronchoscopic challenge) in rhesus macaques influences the distribution of disease but not the overall outcome of the infection (25).…”

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confidence: 99%

Rhesus Macaques Are More Susceptible to Progressive Tuberculosis than Cynomolgus Macaques: a Quantitative Comparison

et al. 2018

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In the past 2 decades, it has become increasingly clear that nonhuman primates, specifically macaques, are useful models for human tuberculosis (TB). Several macaque species have been used for TB studies, and questions remain about the similarities and differences in TB pathogenesis among macaque species, which can complicate decisions about the best species for a specific experiment. Here we provide a quantitative assessment, using serial positron emission tomography and computed tomography (PET-CT) imaging and precise quantitative determination of bacterial burdens of low-dose Mycobacterium tuberculosis infection in cynomolgus macaques of Chinese origin, rhesus macaques of Chinese origin, and Mauritian cynomolgus macaques. This comprehensive study demonstrates that there is substantial variability in the outcome of infection within and among species. Overall, rhesus macaques have higher rates of disease progression, more lung, lymph node, and extrapulmonary involvement, and higher bacterial burdens than Chinese cynomolgus macaques. The small cohort of Mauritian cynomolgus macaques assessed here indicates that this species is more similar to rhesus macaques than to Chinese cynomolgus macaques in terms of M. tuberculosis infection outcome. These data provide insights into the differences among species, providing valuable data to the field for assessing macaque studies of TB.KEYWORDS Mycobacterium, PET CT, macaque, nonhuman primate, tuberculosis N ovel therapeutics for tuberculosis (TB) are greatly needed to curb the 10.4 million new cases and 1.8 million deaths that occur due to this global pandemic (1). Drugs have aided the fight against TB by saving an estimated 49 million lives between 2000 and 2015 (1). However, the current drug regimen is lengthy and cumbersome, and about 480,000 people developed multidrug-resistant TB in 2015 alone (1), so there is much room for improvement. The only licensed vaccine for TB, Mycobacterium bovis bacillus Calmette-Guérin (BCG), protects infants from severe manifestations of TB but does not provide long-lasting immunity against pulmonary TB (2). The urgent need for new therapeutics for TB has driven the development of novel drugs and vaccines that require preclinical evaluation in animal models. Many animal models are used in TB research, including mice, zebra fish, cattle, rabbits, guinea pigs, and nonhuman primates (NHPs) (3, 4). Mice and NHPs are the two animal models that are the most useful, as the other models suffer from a lack of resources available for immunologic studies. Mice have their shortcomings too, as their TB pathology is not fully representative of the pathology observed in humans, and they do not develop human-like latent TB infection (LTBI). NHPs recapitulate the full spectrum of Mycobacterium tuberculosis

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“…The nonhuman primate model of TB mimics all the pathological features of human TB and has the advantage of a large array of available immunologic reagents (3,8,10,11,26). Granulomas of the macaque model exhibit characteristics very similar to human tuberculous granulomas that include cavitation, calcification, caseous necrosis, and multinucleated giant cells within affected lung and lymph nodes.…”

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confidence: 99%

Early Events in Mycobacterium tuberculosis Infection in Cynomolgus Macaques

et al. 2006

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Little is known regarding the early events of infection of humans with Mycobacterium tuberculosis. The cynomolgus macaque is a useful model of tuberculosis, with strong similarities to human tuberculosis. In this study, eight cynomolgus macaques were infected bronchoscopically with low-dose M. tuberculosis; clinical, immunologic, microbiologic, and pathologic events were assessed 3 to 6 weeks postinfection. Gross pathological abnormalities were observed as early as 3 weeks, including Ghon complex formation by 5 weeks postinfection. Caseous granulomas were observed in the lung as early as 4 weeks postinfection. Only caseous granulomas were observed in the lungs at these early time points, reflecting a rigorous initial response. T-cell activation (CD29 and CD69) and chemokine receptor (CXCR3 and CCR5) expression appeared localized to different anatomic sites. Activation markers were increased on cells from airways and only at modest levels on cells in peripheral blood. The priming of mycobacterium-specific T cells, characterized by the production of gamma interferon occurred slowly, with responses seen only after 4 weeks of infection. These responses were observed from T lymphocytes in blood, airways, and hilar lymph node, with responses predominantly localized to the site of infection. From these studies, we conclude that immune responses to M. tuberculosis are relatively slow in the local and peripheral compartments and that necrosis occurs surprisingly quickly during granuloma formation.

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Evidence for a rhesus monkey model of asymptomatic tuberculosis

Cited by 60 publications

References 39 publications

Monkey Models of Tuberculosis: Lessons Learned

Monkey Models of Tuberculosis: Lessons Learned

Rhesus Macaques Are More Susceptible to Progressive Tuberculosis than Cynomolgus Macaques: a Quantitative Comparison

Early Events in Mycobacterium tuberculosis Infection in Cynomolgus Macaques

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