IN VITRO MODELS OF MYCOBACTERIUM TUBERCULOSIS DORMANCY, AND IN VIVO MODELS OF LATENT TUBERCULOSIS INFECTION

2019 ◽  
Vol 64 (5) ◽  
pp. 299-307
Author(s):  
M. V. Fursov ◽  
I. A. Dyatlov ◽  
V. D. Potapov
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
In Vitro Models ◽  
Tuberculosis Infection ◽  
Published Data ◽  
In Vivo Models ◽  
Dormant State

Modeling of tuberculosis infection is carried out in order to clarify various aspects of the tuberculosis pathogenesis, as well as the testing of new anti-tuberculosis drugs. The characteristic of in vitro models (n = 16) for Mycobacterium tuberculosis dormant state and in vivo models (n = 14) for the latent tuberculosis infection involving several animal species published to date are presented in this review. A brief description of the models and the results obtained by the authors are presented. The analysis of the published data reflects the list of methodological procedures that allow researchers to study the mechanism of the transition of M. tuberculosis cells to a dormant state and reverse to metabolically active state, as well as the process of conversion of active tuberculosis infection to a latent tuberculosis and reactivation.

scholarly journals Perbedaan Antara Jumlah Sel T Subset Gamma-Delta di Darah Tepi pada Penderita Tuberkulosis dan Orang dengan Latent Tuberculosis Infection

2016 ◽  
Vol 18 (2) ◽  
pp. 162
Author(s):  
Ryzky Widi Atmaja ◽  
Jusak Nugraha
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Tuberculosis Infection ◽  
Gamma Delta

Abstrak Latar Belakang. Imunitas memiliki peranan penting untuk melindungi host dari bacilli Mycobacterium tuberculosis (M.tb), bakteri Obligat  intraseluler  yang  menyebabkan  Tuberkulosis  (TB)  dan  latent  tuberculosis  infection  (LTBI).  Sel  T  subset  gamma-delta (T-γδ) adalah sel-sel potensial tersembunyi yang bermain peran di imunitas innate dan adaptive pada TB. Tetapi, hingga kini perananya   di   LTBI   masih   menjadi   misteri.   Bahan   dan   Metode.   Penelitian   dilakukan   dengan   melibatkan   10 penderita  TB serta 10 orang dengan LTBI. Mereka didapatkan dari Rumah Sakit Paru Surabaya melalui suatu persetujuan kelaikan etik   dari  Universitas  Airlangga.  Sampel-sampel  tersebut  akan  dihitung  jumlah  sel  T-γδ  menggunakan  F A C S C a l i b u r. Hasil.   Jumlah   sel   T-γδ   meningkat   pada   TB   (10,7%)   dan   LTBI   (15, 4%).   Jumlah   dari   kedua   kelompok   tersebut melebihi   rerata   normal   di   darah   tepi   (1% - 5%).   Kesimpulan.   Penigkatan   jumlah   sel   T-γδ   pada   TB   disebabkan melimpahnya kadar IL-12 yang dilepas oleh makrofag selama infeksi. Sementara, peningkatan jumlah sel T-γδ pada LTBI diasumsikan    karena    banyaknya    heat    shock    protein    (HSPs)    yang    dilepas    oleh    M.tb    di    bawah    kondisi    stres. ...Kata  kunci:  tuberkulosis,  latent  tuberculosis  infection,  Mycobacterium  tuberclosis,  sel  T  subset  gamma-d e l t a.

scholarly journals Prevalence of Latent Tuberculosis Infection in the Middle East and North Africa: A Systematic Review

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Mazin Barry
Keyword(s):  
Systematic Review ◽  
Middle East ◽  
North Africa ◽  
Subgroup Analysis ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Tuberculosis Infection ◽  
World Health ◽  
Published Data ◽  
Mena Region

Objective. Data on the prevalence of latent tuberculosis infection (LTBI) in Middle Eastern and North African countries are scarce. We aimed to review all relevant published data in countries belonging to this region to determine the overall prevalence of LTBI in the Middle East and North Africa (MENA) region. Methods. In this systematic review PubMed and Google Scholar databases were searched for observational, prospective, retrospective, cross-sectional, and cohort studies providing prevalence data of LTBI in any MENA country. Studies fulfilling the search criteria were incorporated in the review. Overall prevalence of LTBI with 95% confidence intervals (CI) was calculated using the random-effects model; heterogeneity was assessed using I 2 statistics. Gender and age group-based subgroup analyses were performed to evaluate the basis of heterogeneity. Results. The total number of overall LTBI studies identified was 956, of which 31 studies from ten countries within the MENA region were included that represented 12,439 subjects. The overall prevalence was 41.78% (95% CI 31.18% to 52.78%, I 2 = 99.31 % ). By gender-based subgroup analysis, the prevalence of LTBI was 33.12% (95% CI 18.97% to 49.04%, I 2 = 99.25 % ) and 32.65% (95% CI 19.79% to 47%, I 2 = 98.89 % ) in males and females, respectively, while in the age-based subgroup analysis, the prevalence of LTBI was 0.44% (95% CI -0.05% to 0.9%), 3.37% (95% CI 2.23% to 4.74%, I 2 = 0 % ), and 43.81% (95% CI 33.09% to 54.82%, I 2 = 99.18 % ) for children, adolescents, and adults, respectively. Conclusion. This systematic review reveals a high prevalence of LTBI in the MENA region; enhanced LTBI surveillance and prompt infection prevention steps are urgently needed to prevent active tuberculosis, this would help achieve the World Health Organization End TB Strategy 2035, and the United Nations Sustainable Development Goals 2030 target in the MENA region.

scholarly journals Bioreactors as physiologicallike in vitro models

2020 ◽  
Author(s):  
Sara Mantero ◽  
Federica Boschetti
Keyword(s):  
Culture Conditions ◽  
In Vitro Models ◽  
In Vivo Models ◽  
In Vitro Development ◽  
Culture Cells ◽  
Vitro Development ◽  
Tissue Models ◽  
Mechanical Stretching

Bioreactors are powerful tools for in vitro development of engineered substitutes through controlled biological, physical, and mechanical culture conditions: bioreactor technology allows a closer in vitro replication of native tissues. One of bioreactors applications is the design of in vitro 3D tissue models as a bridge between 2D and in vivo models, allowing the application of 3R (replacement, reduction, refinement) principle. To this aim, bioreactors can be used to culture cells seeded on engineered scaffolds under in vivo-like conditions. Another key use of bioreactors is for perfusion decellularization of tissues and organs to be used as scaffolds. This contribution describes a dynamic stretching. bioreactor, imposing a mechanical stretching to the cultured constructs, allowing the development of skeletal muscle engineered constructs, and a decellularization bioreactor, designed for decellularization of blood vessels.

scholarly journals MicroRNA-889 Inhibits Autophagy To Maintain Mycobacterial Survival in Patients with Latent Tuberculosis Infection by Targeting TWEAK

mBio ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Der-Yuan Chen ◽  
Yi-Ming Chen ◽  
Chin-Fu Lin ◽  
Che-Min Lo ◽  
Hung-Jen Liu ◽  
...  
Keyword(s):  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Granuloma Formation ◽  
Tuberculosis Infection ◽  
Renal Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antibody Treatment ◽  
Content Type ◽  
Tnf Α

ABSTRACT Autophagy plays an important role in protecting the host against pathogens. Mycobacterium tuberculosis can suppress autophagy and then remain dormant and survive within the host for an extended period, which is responsible for latent tuberculosis infection (LTBI). Here, we explored the role of microRNAs (miRNAs) in LTBI. The miRNA profiles were explored using the next-generation sequencing approach, followed by quantitative reverse transcription-PCR validation. The biological function of candidate miRNA was evaluated using immunoblotting, immunofluorescence techniques, and enzyme-linked immunosorbent assay in an in vitro human TB granuloma model. An increased miR-889 expression was observed in patients with LTBI compared with that in patients without infection. The reporter assay identified tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) as the target of miR-889. Mycobacterial infection induced TWEAK upregulation in the early phase. TWEAK induced autophagy and promoted mycobacterial autophagosome maturation through activation of AMP-activated protein kinase (AMPK). Upon entry to LTBI status, elevated miR-889 levels were associated with TNF alpha (TNF-α) and granuloma formation/maintenance. MiR-889 inhibited autophagy via posttranscriptional suppression of TWEAK expression to maintain mycobacterial survival in granulomas. Adalimumab (anti-TNF-α monoclonal antibody) treatment reduced levels of both TNF-α and miR-889 and caused granuloma destruction and LTBI reactivation. The circulating miR-889 and TWEAK levels were correlated with LTBI and subsequently associated with anti-TNF-α-related LTBI reactivation in patients. We propose that miR-889 and TWEAK can act as targets that can be manipulated for antimycobacterial therapeutic purposes and act as candidate biomarkers for LTBI and LTBI reactivation, respectively. IMPORTANCE TB remains a leading cause of morbidity and mortality worldwide. Approximately one-quarter of the world’s population has latent TB infection. TWEAK is a multiple-function cytokine and may be used as a target for the treatment of rheumatic diseases, cardiovascular diseases, and renal diseases. Here, we demonstrated a novel relationship between TWEAK and activation of the autophagic machinery which promotes antimycobacterial immunity. Additionally, TB infection is highly dynamic and determined by the interaction between the host and mycobacterium. We demonstrated a mechanism of fine-tuned balance between the mycobacterium and host for granuloma formation and/or maintenance in LTBI status. Once patients entered LTBI status, the upregulation of miR-889 was associated with TNF-α levels and granuloma formation to maintain mycobacterial survival. Adalimumab (a TNF-α inhibitor) reduced both TNF-α and miR-889 levels and caused LTBI reactivation and, thus, TWEAK enhancement. MiR-889 and TWEAK may become potential diagnostic biomarkers or therapeutic targets for LTBI and LTBI reactivation, respectively.

scholarly journals Functional Studies on Viable Circulating Tumor Cells

2016 ◽  
Vol 62 (2) ◽  
pp. 328-334 ◽  
Author(s):  
Klaus Pantel ◽  
Catherine Alix-Panabières
Keyword(s):  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Diagnostics ◽  
Published Data ◽  
Liquid Biopsies ◽  
In Vivo Models ◽  
Functional Studies

AbstractBACKGROUNDResearch on circulating tumor cells (CTCs) as new biomarkers has received great attention over the past decade. In particular, the capture and analysis of CTCs as “liquid biopsies” provides the possibility to avoid invasive tissue biopsies, with obvious implications in cancer diagnostics.CONTENTThe focus of this review is to describe and discuss how functional studies on viable CTCs can enlarge the spectrum of applications of liquid biopsies, with emphasis on breast, prostate, colon, and lung cancer as the major tumor entities in industrialized countries. The low number of CTCs in the peripheral blood of most cancer patients makes challenging the in vitro culture of CTCs. Epithelial tumor cells are difficult to culture, even when starting with millions of tumor cells. Recently, several groups have achieved important advances in the in vitro and in vivo expansion of CTCs from cancer patients at very advanced stages with higher amounts of CTCs. Here, we present current technologies to enrich and detect viable human CTCs, including positive and negative enrichment strategies that are based on antigen expression and physical properties of CTCs. We also discuss published data about functional studies on CTCs that use in vitro and in vivo models.SUMMARYFunctional analyses on CTCs offer the possibility to identify the biological properties of metastatic cells, including the identification of metastasis-initiating cells. Moreover, CTC-derived cell lines and xenografts might reveal new therapeutic targets and can be used for drug screening.

Treatment of latent tuberculosis infection induces changes in multifunctional Mycobacterium tuberculosis-specific CD4+ T cells

2015 ◽  
Vol 205 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Ilaria Sauzullo ◽  
Fabio Mengoni ◽  
Claudia Mascia ◽  
Raffaella Rossi ◽  
Miriam Lichtner ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Cd4 T Cells ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Tuberculosis Infection

scholarly journals Transcription of Genes Involved in Sulfolipid and Polyacyltrehalose Biosynthesis of Mycobacterium tuberculosis in Experimental Latent Tuberculosis Infection

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e58378 ◽  
Author(s):  
Jimmy E. Rodríguez ◽  
Ana S. Ramírez ◽  
Laura P. Salas ◽  
Cecilia Helguera-Repetto ◽  
Jorge Gonzalez-y-Merchand ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Tuberculosis Infection

scholarly journals Experimental Models in Rheumatoid Arthritis:

2020 ◽  
Vol 8 (1) ◽  
pp. 119-134
Author(s):  
Verônica Assalin Zorgetto-Pinheiro ◽  
Alexandre Meira de Vasconcelos ◽  
Rafael Sanaiotte Pinheiro ◽  
Danielle Bogo ◽  
Iandara Schettert Silva
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Testing ◽  
Pathological Condition ◽  
In Vitro Models ◽  
Experimental Models ◽  
In Vivo Models ◽  
Methodological Tool ◽  
Class 1

Rheumatoid arthritis is an autoimmune and chronic pathological condition characterized by an inflammatory process of the joints It is a complex and multifactorial, involving genetic, epigenetic and environmental factors and the use of experimental models is required to better understand its pathology and for drug testing. The aim of this study was to perform a systematic literature review on experimental models in rheumatoid arthritis using IRAMUTEQ, a software that analysis, qualitatively and quantitatively, text fragments, as a methodological tool. After searching for articles published in the last five years on Scopus database and applying the exclusion criteria, we ended with 84 articles. The most commonly employed experimental models was the arthritis induction by inoculation of the Complete Freund's Adjuvant (CFA), followed by the use of combined methodologies and the collagen-induced arthritis (CIA). The analyses of abstracts by the IRAMUTEQ software provided a classification according to their textual elements in four classes, which were grouped into three main themes: in vivo models (class 1), clinical practice and traditional medicine (classes 2 and 3) and in vitro models (class 4) and it was also possible to build a similarity tree of the terms present in the abstracts and a word cloud with the most cited terms. Thus, the use of the IRAMUTEQ software as a methodological tool has been satisfactory, since it was possible to identify the main experimental models used, keywords, pathological processes and molecules involved in the pathogenesis of rheumatoid arthritis free of the researchers’ bias, in addition to being a tool for visual and intuitive results.

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