Badger macrophages fail to produce nitric oxide, a key anti-mycobacterial effector molecule

Bilham, Kirstin; Boyd, Amy; Preston, Stephen G.; Buesching, Christina D.; Newman, Chris; Macdonald, David W.; Smith, Adrian L.

doi:10.1038/srep45470

Cited by 12 publications

(9 citation statements)

References 74 publications

(80 reference statements)

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“…Different research groups have frequently observed the complete or partial failure of macrophages in producing NO − in cultures containing fetal bovine serum (FBS). The MDM from humans, cattle, sheep, goats, badgers, and ferrets in a culture containing FBS were found to be unable to produce a detectable level of NO − or approximately 20-to 50-fold less than macrophages from chickens (Denis, 1994;Dumarey et al, 1994;Arias et al, 1997;Ohki et al, 1999;Sacco et al, 2006;Zelnickova et al, 2008;Khalifeh et al, 2009;Guimarães et al, 2011;Azevedo et al, 2016;Bilham et al, 2017;Garcia et al, 2017). The FBS contains a considerable amount of immuno-regulatory cytokines and bioactive molecules.…”

Section: Discussionmentioning

confidence: 99%

The effect of host genetics on in vitro performance of bovine monocyte-derived macrophages

Emam

Tabatabaei

Sargolzaei

et al. 2019

Journal of Dairy Science

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The dynamic interaction between the host and pathogens, along with environmental factors, influences the regulation of mammalian immune responses. Therefore, comprehensive in vivo immune-phenotyping during an active response to a pathogen can be complex and prone to confounding effects. Evaluating critical fundamental aspects of the immune system at a cellular level is an alternative approach to reduce this complexity. Therefore, the objective of the current study was to examine an in vitro model for functional phenotyping of bovine monocyte-derived macrophages (MDM), cells which play a crucial role at all phases of inflammation, as well influence downstream immune responses. As indicators of MDM function, phagocytosis and nitric oxide (NO −) production were tested in MDM of 16 cows in response to 2 common bacterial pathogens of dairy cows, Escherichia coli and Staphylococcus aureus. Notable functional variations were observed among the individuals (coefficient of variation: 33% for phagocytosis and 70% in the production of NO −). The rank correlation analysis revealed a significant, positive, and strong correlation (rho = 0.92) between NO − production in response to E. coli and S. aureus, and a positive but moderate correlation (rho = 0.58) between phagocytosis of E. coli and S. aureus. To gain further insight into this trait, another 58 cows were evaluated solely for NO − response against E. coli. The pedigree of the tested animals was added to the statistical model and the heritability was estimated to be 0.776. Overall, the finding of this study showed a strong effect of host genetics on the in vitro activities of MDM and the possibility of ranking Holstein cows based on the in vitro functional variation of MDM.

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Section: Discussionmentioning

confidence: 99%

The effect of host genetics on in vitro performance of bovine monocyte-derived macrophages

Emam

Tabatabaei

Sargolzaei

et al. 2019

Journal of Dairy Science

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“…It is plausible to hypothesize, that evolutionary adaption of the badger to a subterranean lifestyle contributes to its tolerance of environmental dust inhalation. Further, a recent in vitro study demonstrated, that badger macrophages fail to produce nitric oxide (NO) [ 37 ]. This free radical is an important anti-mycobacterial effector molecule, and was previously shown to be upregulated in an in vivo rat model of silica inhalation [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Environmental dust inhalation in the European badger (Meles meles): Systemic distribution of silica-laden macrophages, pathological changes, and association with Mycobacterium bovis infection status

et al. 2018

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Chronic inhalation of crystalline silica and silicates may lead to severe lung disease in humans, termed silicosis. The disease is an occupational health concern in miners and related professions worldwide. Silicosis is also a strong risk factor for tuberculosis in humans. Due to its subterranean lifestyle, the European badger (Meles meles) is continuously exposed to environmental dust, while this species is also susceptible to tuberculosis, caused by Mycobacterium bovis. To date, a thorough investigation of mineral dust retention and its possible implication as a risk factor for mycobacterial infection in badgers has not been performed. The aims of this retrospective histological study were (1) to describe the systemic tissue distribution of silica-laden macrophages (SLMs) in badgers; (2) to compare the amount of SLMs in tissues of badgers of differing M. bovis infection status, pulmonary SLM burden and age; and (3) to assess whether inflammation was associated with SLMs. We assessed lung, lymph nodes, liver and spleen of 60 wild-caught badgers of known M. bovis infection status for the presence of SLMs using polarizing light microscopy. SLMs were consistently present within the lungs and were widely distributed throughout the lymphatic system. No inflammatory reaction to SLMs, as occurs in human silicosis, was observed in any tissue. Distribution and amount of SLMs were similar between M. bovis positive and negative badgers, and we were not able to show an association between the amount of SLMs and M. bovis infection status. The amount of SLMs within intra- and extrathoracic lymph nodes was positively associated with the amount of pulmonary SLMs, and with age. This is the first report of substantial and systemic tissue retention of mineral dust particles in a mammalian species lacking associated chronic inflammation (i.e. silicosis). We further highlight different pathogenetic mechanisms underlying silicosis and benign SLM accumulations following siliceous dust inhalation.

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“…Nitric oxide (NO) is produced through oxidation of l -arginine ( 50 ) in a reaction catalyzed by an inducible nitric oxide synthase (iNOS) ( 51 ). However, studies in badgers have revealed that blood monocyte-derived macrophages do not produce NO or upregulate iNOS expression following in vitro activation of macrophages ( 52 ). This intriguing finding might imply that badgers should lack the ability to control infection via the innate response, though there is no strong pathological evidence to support this.…”

Section: Pathogenesis Of Tuberculosis In Badgersmentioning

confidence: 99%

Pathogenesis of Mycobacterium bovis Infection: the Badger Model As a Paradigm for Understanding Tuberculosis in Animals

Gormley

Corner

2018

Front. Vet. Sci.

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Tuberculosis in animals is caused principally by infection with Mycobacterium bovis and the potential for transmission of infection to humans is often the fundamental driver for surveillance of disease in livestock and wild animals. However, with such a vast array of species susceptible to infection, it is often extremely difficult to gain a detailed understanding of the pathogenesis of infection--a key component of the epidemiology in all affected species. This is important because the development of disease control strategies in animals is determined chiefly by an understanding of the epidemiology of the disease. The most revealing data from which to formulate theories on pathogenesis are that observed in susceptible hosts infected by natural transmission. These data are gathered from detailed studies of the distribution of gross and histological lesions, and the presence and distribution of infection as determined by highly sensitive bacteriology procedures. The information can also be used to establish the baseline for evaluating experimental model systems. The European badger (Meles meles) is one of a very small number of wild animal hosts where detailed knowledge of the pathogenesis of M. bovis infection has been generated from observations in natural-infected animals. By drawing parallels from other animal species, an experimental badger infection model has also been established where infection of the lower respiratory tract mimics infection and the disease observed in natural-infected badgers. This has facilitated the development of diagnostic tests and testing of vaccines that have the potential to control the disease in badgers. In this review, we highlight the fundamental principles of how detailed knowledge of pathogenesis can be used to evaluate specific intervention strategies, and how the badger model may be a paradigm for understanding pathogenesis of tuberculosis in any affected wild animal species.

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Badger macrophages fail to produce nitric oxide, a key anti-mycobacterial effector molecule

Cited by 12 publications

References 74 publications

The effect of host genetics on in vitro performance of bovine monocyte-derived macrophages

The effect of host genetics on in vitro performance of bovine monocyte-derived macrophages

Environmental dust inhalation in the European badger (Meles meles): Systemic distribution of silica-laden macrophages, pathological changes, and association with Mycobacterium bovis infection status

Pathogenesis of Mycobacterium bovis Infection: the Badger Model As a Paradigm for Understanding Tuberculosis in Animals

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