Fate of Mycobacterium tuberculosis in peroxidase-loaded resting murine macrophages

Mendoza-Aguilar, Melby; Arce‐Paredes, Patricia; Aquino-Vega, Mayda; Rodríguez‐Martínez, Sandra; Rojas-Espinosa, O

doi:10.1016/j.ijmyco.2012.11.002

Cited by 7 publications

(10 citation statements)

References 28 publications

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“…[51][52][53] The presence of active MPO and ROS in our study suggested that NETs might have microbicidal activity on the microorganism; however, we were unable to demonstrate any microbicidal activity of the in vivo-induced NETs on M. tuberculosis. Resistance of this microorganism to the microbicidal activity of NETs could be explained by the multiple detoxifying mechanisms possessed by this bacterium, as emphasized by Mendoza-Aguilar et al 53 It is also probably that M. tuberculosis uses the extracellular DNA to produce biofilms which can be later used as a nourishment. Very early (2 h) following its intradermal injection in guinea pigs, M. tuberculosis caused a noticeable accumulation of neutrophils that released NETs.…”

Section: Discussionmentioning

confidence: 85%

In vivoinduction of neutrophil extracellular traps byMycobacterium tuberculosisin a guinea pig model

et al. 2017

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In 2004, a novel mechanism of cellular death, called 'NETosis', was described in neutrophils. This mechanism, different from necrosis and apoptosis, is characterized by the release of chromatin webs admixed with microbicidal granular proteins and peptides (NETs). NETs trap and kill a variety of microorganisms. Diverse microorganisms, including Mycobacterium tuberculosis, are NET inducers in vitro. The aim of this study was to examine whether M. tuberculosis can also induce NETs in vivo and if the NETs are bactericidal to the microorganism. Guinea pigs were intradermally inoculated with M. tuberculosis H37Rv, and the production of NETs was investigated at several time points thereafter. NETs were detected as early as 30 min post-inoculation and were clearly evident by 4 h post-inoculation. NETs produced in vivo contained DNA, myeloperoxidase, elastase, histones, ROS and acid-fast bacilli. Viable and heat-killed M. tuberculosis, as well as Mycobacterium bovis BCG were efficient NET inducers, as were unilamellar liposomes prepared with lipids from M. tuberculosis. In vitro, guinea pig neutrophils also produced NETs in response to M. tuberculosis. However, neither the in vivo nor the in vitro-produced NETs were able to kill M. tuberculosis. Nevertheless, in vivo, neutrophils might propitiate recruitment and activation of more efficient microbicidal cells.

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Section: Discussionmentioning

confidence: 85%

In vivoinduction of neutrophil extracellular traps byMycobacterium tuberculosisin a guinea pig model

et al. 2017

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“…Also the nucleus becomes smaller; most organelles surround a small intact nucleus in a narrow rim of cytoplasm [ 60 – 62 ]. Interestingly, there are several lines of evidences which indicate the killing of mycobacteria via single members of reactive oxygen species (nitric oxide [ 63 ], peroxide [ 64 ] and reactive nitrogen intermediates [ 65 ]).…”

Section: Discussionmentioning

confidence: 99%

Mycobacteria infect different cell types in the human lung and cause species dependent cellular changes in infected cells

et al. 2016

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BackgroundMycobacterial infections remain a significant cause of morbidity and mortality worldwide. Due to limitations of the currently available model systems, there are still comparably large gaps in the knowledge about the pathogenesis of these chronic inflammatory diseases in particular with regard to the human host. Therefore, we aimed to characterize the initial phase of mycobacterial infections utilizing a human ex vivo lung tissue culture model designated STST (Short-Term Stimulation of Tissues).MethodsHuman lung tissues from 65 donors with a size of 0.5–1 cm3 were infected each with two strains of three different mycobacterial species (M. tuberculosis, M. avium, and M. abscessus), respectively. In order to preserve both morphology and nucleic acids, the HOPE® fixation technique was used. The infected tissues were analyzed using histo- and molecular-pathological methods. Immunohistochemistry was applied to identify the infected cell types.ResultsMorphologic comparisons between ex vivo incubated and non-incubated lung specimens revealed no noticeable differences. Viability of ex vivo stimulated tissues demonstrated by TUNEL-assay was acceptable. Serial sections verified sufficient diffusion of the infectious agents deep into the tissues. Infection was confirmed by Ziel Neelsen-staining and PCR to detect mycobacterial DNA. We observed the infection of different cell types, including macrophages, neutrophils, monocytes, and pneumocytes-II, which were critically dependent on the mycobacterial species used. Furthermore, different forms of nuclear alterations (karyopyknosis, karyorrhexis, karyolysis) resulting in cell death were detected in the infected cells, again with characteristic species-dependent differences.ConclusionWe show the application of a human ex vivo tissue culture model for mycobacterial infections. The immediate primary infection of a set of different cell types and the characteristic morphologic changes observed in these infected human tissues significantly adds to the current understanding of the initial phase of human pulmonary tuberculosis. Further studies are ongoing to elucidate the molecular mechanisms involved in the early onset of mycobacterial infections in the human lung.

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“…The production of ROS, O 2 − , H 2 O 2 , and HOCl by phagocytic cells in response to infection is a highly effective microbicidal mechanism that is also referred to as a respiratory burst. In contrast to neutrophils, mature macrophages contain much less concentrations of MPO and thus are unable to kill pathogenic intracellular microorganisms by this system [18].…”

Section: Mycobacteria: the Smart Pathogensmentioning

confidence: 99%

Iron Supplementation Therapy, A Friend and Foe of Mycobacterial Infections?

Agoro

Mura

2019

Pharmaceuticals

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Iron is an essential element that is required for oxygen transfer, redox, and metabolic activities in mammals and bacteria. Mycobacteria, some of the most prevalent infectious agents in the world, require iron as growth factor. Mycobacterial-infected hosts set up a series of defense mechanisms, including systemic iron restriction and cellular iron distribution, whereas mycobacteria have developed sophisticated strategies to acquire iron from their hosts and to protect themselves from iron’s harmful effects. Therefore, it is assumed that host iron and iron-binding proteins, and natural or synthetic chelators would be keys targets to inhibit mycobacterial proliferation and may have a therapeutic potential. Beyond this hypothesis, recent evidence indicates a host protective effect of iron against mycobacterial infections likely through promoting remodeled immune response. In this review, we discuss experimental procedures and clinical observations that highlight the role of the immune response against mycobacteria under various iron availability conditions. In addition, we discuss the clinical relevance of our knowledge regarding host susceptibility to mycobacteria in the context of iron availability and suggest future directions for research on the relationship between host iron and the immune response and the use of iron as a therapeutic agent.

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Fate of Mycobacterium tuberculosis in peroxidase-loaded resting murine macrophages

Abstract: The lack of granular MPO in mature macrophages, and the predilection of mycobacteria to infect these cells are two situations that favor the development of tuberculosis and related diseases, such as leprosy and Buruli ulcer.

Cited by 7 publications

References 28 publications

In vivoinduction of neutrophil extracellular traps byMycobacterium tuberculosisin a guinea pig model

In vivoinduction of neutrophil extracellular traps byMycobacterium tuberculosisin a guinea pig model

Mycobacteria infect different cell types in the human lung and cause species dependent cellular changes in infected cells

Iron Supplementation Therapy, A Friend and Foe of Mycobacterial Infections?

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