Radiologic Responses in Cynomolgus Macaques for Assessing Tuberculosis Chemotherapy Regimens

Lin, Philana Ling; Coleman, Teresa; Carney, Jonathan; Lopresti, Brian J.; Tomko, Jaime; Fillmore, Dan; Dartois, Véronique; Scanga, Charles A.; Frye, L. James; Christopher, J; Klein, Edwin; Barry, Clifton E.; Flynn, JoAnne L.

doi:10.1128/aac.00277-13

Cited by 160 publications

(266 citation statements)

References 31 publications

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“…CD, cluster of differentiation; HLA-DR, human leukocyte antigen-antigen D related. spectrum of granuloma types seen both by histopathology (e.g., caseous, fibrotic, nonnecrotizing) and bacterial burden (4,21,22), and a range of radiographic patterns and inflammatory responses in the lung seen by modern 2-deoxy-2-[ 18 F]-fluoro-D-glucose positron emission tomography/computed tomography (PET/CT) imaging of the thorax (23)(24)(25). Importantly, both humans and macaques develop a spectrum of latent infection (4,22,26).…”

Section: Discussionmentioning

confidence: 99%

Diversity of Human and Macaque Airway Immune Cells at Baseline and during Tuberculosis Infection

Silver

Myers

Jarvela

et al. 2016

Am J Respir Cell Mol Biol

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Immune cells of the distal airways serve as "first responders" of host immunity to the airborne pathogen Mycobacterium tuberculosis (Mtb). Mtb infection of cynomolgus macaques recapitulates the range of human outcomes from clinically silent latent tuberculosis infection (LTBI) to active tuberculosis of various degrees of severity. To further advance the application of this model to human studies, we compared profiles of bronchoalveolar lavage (BAL) cells of humans and cynomolgus macaques before and after Mtb infection. A simple gating strategy effectively defined BAL T-cell and phagocyte populations in both species. BAL from Mtb-naive humans and macaques showed similar differential cell counts. BAL T cells of macaques were composed of fewer CD41 cells but more CD81 and CD4 1 CD8 1 double-positive cells than were BAL T cells of humans. The most common mononuclear phagocyte population in BAL of both species displayed coexpression of HLA-DR, CD206, CD11b, and CD11c; however, multiple phagocyte subsets displaying only some of these markers were observed as well. Macaques with LTBI displayed a marked BAL lymphocytosis that was not observed in humans with LTBI. In macaques, the prevalence of specific mononuclear phagocyte subsets in baseline BAL correlated with ultimate outcomes of Mtb infection (i.e., LTBI versus active disease).Overall, these findings demonstrate the comparability of studies of pulmonary immunity to Mtb in humans and macaques. They also indicate a previously undescribed complexity of airway mononuclear phagocyte populations that suggests further lines of investigation relevant to understanding the mechanisms of both protection from and susceptibility to the development of active tuberculosis within the lung.

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Section: Discussionmentioning

confidence: 99%

Diversity of Human and Macaque Airway Immune Cells at Baseline and during Tuberculosis Infection

Silver

Myers

Jarvela

et al. 2016

Am J Respir Cell Mol Biol

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“…These experiments revealed two things: (1) Granuloma formation might actually aid bacterial proliferation, because accelerated bacterial proliferation coincides with granuloma formation (Lesley and Ramakrishnan 2008); and (2) early granulomas are not fixed in size and location. Subsequently, TB studies in mice and nonhuman primates further supported the notion that granulomas are actually highly dynamic structures (Egen et al 2008;Lin et al 2013;Ramakrishnan 2013).…”

Section: Dynamic Granulomasmentioning

confidence: 92%

Animal Models of Tuberculosis: Zebrafish

Leeuwen

Sar

Bitter

2014

Cold Spring Harbor Perspectives in Medicine

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Correspondence: a.vandersar@vumc.nl Over the past decade the zebrafish (Danio rerio) has become an attractive new vertebrate model organism for studying mycobacterial pathogenesis. The combination of mediumthroughput screening and real-time in vivo visualization has allowed new ways to dissect host pathogenic interaction in a vertebrate host. Furthermore, genetic screens on the host and bacterial sides have elucidated new mechanisms involved in the initiation of granuloma formation and the importance of a balanced immune response for control of mycobacterial pathogens. This article will highlight the unique features of the zebrafish-Mycobacterium marinum infection model and its added value for tuberculosis research.

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“…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%

“…Macaque models for TB drug evaluation. Finally, another recently reported investigation of experimental M. tuberculosis infection in a CM model was also published from the University of Pittsburgh School of Medicine (56,57). The purpose of this research endeavor was to determine potential alternative markers for evaluating the efficacy of TB drugs.…”

Section: Specific Macaque Models Of Tbmentioning

confidence: 99%

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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Radiologic Responses in Cynomolgus Macaques for Assessing Tuberculosis Chemotherapy Regimens

Cited by 160 publications

References 31 publications

Diversity of Human and Macaque Airway Immune Cells at Baseline and during Tuberculosis Infection

Diversity of Human and Macaque Airway Immune Cells at Baseline and during Tuberculosis Infection

Animal Models of Tuberculosis: Zebrafish

Monkey Models of Tuberculosis: Lessons Learned

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