A Rhesus Macaque Model of Pulmonary Nontuberculous Mycobacterial Disease

Winthrop, Kevin; Rivera, Andrea; Engelmann, Flora; Rose, Sasha J.; Lewis, Anne D.; Ku, Jennifer; Bermudez, Luiz E.; Messaoudi, Ilhem

doi:10.1165/rcmb.2015-0256rc

Cited by 14 publications

(25 citation statements)

References 28 publications

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“…For instance, IL-18 has been shown to activate NK cells and stimulate IFNγ production during influenza infection in the lungs 46 . Increases in IL-6 and IFNγ have also been observed in nasopharyngeal lavage samples taken from influenza patients, BAL samples taken from flu infected rhesus macaques, and BAL samples from rhesus macaques infected with pulmonary nontuberculous mycobacteria 47 48 49 . The sources of these factors could be alveolar macrophages and lung epithelial cells as previously reported during influenza infection and lung injury 50 51 .…”

Section: Discussionmentioning

confidence: 85%

Genomic and functional analysis of the host response to acute simian varicella infection in the lung

Arnold

Girke

Sureshchandra

et al. 2016

Sci Rep

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Varicella Zoster Virus (VZV) is the causative agent of varicella and herpes zoster. Although it is well established that VZV is transmitted via the respiratory route, the host-pathogen interactions during acute VZV infection in the lungs remain poorly understood due to limited access to clinical samples. To address these gaps in our knowledge, we leveraged a nonhuman primate model of VZV infection where rhesus macaques are intrabronchially challenged with the closely related Simian Varicella Virus (SVV). Acute infection is characterized by immune infiltration of the lung airways, a significant up-regulation of genes involved in antiviral-immunity, and a down-regulation of genes involved in lung development. This is followed by a decrease in viral loads and increased expression of genes associated with cell cycle and tissue repair. These data provide the first characterization of the host response required to control varicella virus replication in the lung and provide insight into mechanisms by which VZV infection can cause lung injury in an immune competent host.

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Section: Discussionmentioning

confidence: 85%

Genomic and functional analysis of the host response to acute simian varicella infection in the lung

Arnold

Girke

Sureshchandra

et al. 2016

Sci Rep

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“…As stated by Winthrop et al ., “studies of NTM pathogenesis and host immunity to NTM have been hampered by the lack of a robust animal model that can mimic human non-disseminated MAC pulmonary disease” [ 39 ]. Studies in non-human primates such as rhesus macaques could be a solution, but our results show that an intranasal infection of BALB/c mice with a properly selected avirulent strain such as the Mah MST 91 could be a valuable alternative.…”

Section: Discussionmentioning

confidence: 99%

Virulence and immunogenicity of genetically defined human and porcine isolates of M. avium subsp. hominissuis in an experimental mouse infection

et al. 2017

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Mycobacterium avium subsp. hominissuis (Mah) represents a health concern for humans and to a lesser extent for pigs, but its zoonotic potential remains elusive. Using multispacer sequence typing (MST) we previously identified 49 different genotypes of Mah among Belgian clinical and porcine isolates, with 5 MSTs shared by both hosts. Using experimental intranasal infection of BALB/c mice, we compared the virulence and immunogenicity of porcine and clinical human isolates with shared genotype or with a genotype only found in humans or pigs. Bacterial replication was monitored for 20 weeks in lungs, spleen and liver and mycobacteria specific spleen cell IFN-γ, IL-10 and IL-17 production as well as serum antibody responses were analyzed. Isolates varied in virulence, with human and porcine isolates sharing MST22 genotype showing a thousand fold higher bacterial replication in lungs and more dissemination to spleen and liver than the human and porcine MST91 isolates. Virulent MST22 type was also associated with progressive suppression of IFN-γ and IL-17 responses, and increased IL-10 production. Whole genome sequencing of the two virulent isolates with MST22 genotype and two avirulent isolates of genotype MST91 and comparison with two well-studied M. avium subsp. hominissuis reference strains i.e. Mah 104 and Mah TH135, identified in the two MST22 isolates nine specific virulence factors of the mammalian cell entry family, that were identical with Mah 104 strain. Despite the obvious limitations of the mouse model, a striking link of virulence and identity at the genome level of porcine and human isolates with the same multisequence type, for which no correlation of place of residence (humans) or farm of origin (pigs) was observed, seems to point to the existence in the environment of certain genotypes of Mah which may be more infectious both for humans and pigs than other genotypes.

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“…It is also worth mentioning the attempts of some authors to investigate nonhuman primates as a model of NTM pulmonary disease [ 188 , 189 ]. Although cost consideration makes these studies hardly practicable for large samples, immunecompetent monkeys could provide a unique opportunity for immunity research and drug development against age and gender-related NTM disease.…”

Section: Animal Models In Preclinical Drug Developmentmentioning

confidence: 99%

Preclinical Models of Nontuberculous Mycobacteria Infection for Early Drug Discovery and Vaccine Research

et al. 2020

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Nontuberculous mycobacteria (NTM) represent an increasingly prevalent etiology of soft tissue infections in animals and humans. NTM are widely distributed in the environment and while, for the most part, they behave as saprophytic organisms, in certain situations, they can be pathogenic, so much so that the incidence of NTM infections has surpassed that of Mycobacterium tuberculosis in developed countries. As a result, a growing body of the literature has focused attention on the critical role that drug susceptibility tests and infection models play in the design of appropriate therapeutic strategies against NTM diseases. This paper is an overview of the in vitro and in vivo models of NTM infection employed in the preclinical phase for early drug discovery and vaccine development. It summarizes alternative methods, not fully explored, for the characterization of anti-mycobacterial compounds.

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A Rhesus Macaque Model of Pulmonary Nontuberculous Mycobacterial Disease

Cited by 14 publications

References 28 publications

Genomic and functional analysis of the host response to acute simian varicella infection in the lung

Genomic and functional analysis of the host response to acute simian varicella infection in the lung

Virulence and immunogenicity of genetically defined human and porcine isolates of M. avium subsp. hominissuis in an experimental mouse infection

Preclinical Models of Nontuberculous Mycobacteria Infection for Early Drug Discovery and Vaccine Research

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