Establishment of A Guinea Pig Model of Latent Tuberculosis with GFP-introduced Mycobacterium Tuberculosis

Sugawara, Isamu; Udagawa, Tadashi; Aoki, Toshiaki; Mizuno, Satoru

doi:10.1620/tjem.219.257

Cited by 9 publications

(4 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, requirement of Biosafety level-3 (BSL-3) facilities and high maintenance cost limits their usage in many resource limited settings of developing world. Other routes of infection such as subcutaneous, intravenous and intranasal have been investigated in other studies for development of TB model in animals ( 6 , 7 , 8 ). Although subcutaneous route may not mimic actual development of infection in animals, however, it can be used as convenient alternative to aerosol route ( 9 , 10 ) in resource limited settings.…”

Section: Introductionmentioning

confidence: 99%

Investigation of Immune Biomarkers Using Subcutaneous Model of M. tuberculosis Infection in BALB/c Mice: A Preliminary Report

et al. 2015

View full text Add to dashboard Cite

Evaluation and screening of vaccines against tuberculosis depends on development of proper cost effective disease models along with identification of different immune markers that can be used as surrogate endpoints of protection in preclinical and clinical studies. The objective of the present study was therefore evaluation of subcutaneous model of M.tuberculosis infection along with investigation of different immune biomarkers of tuberculosis infection in BALB/c mice. Groups of mice were infected subcutaneously with two different doses : high (2×106 CFU) and low doses (2×102 CFU) of M.tuberculosis and immune markers including humoral and cellular markers were evaluated 30 days post M.tuberculosis infections. Based on results, we found that high dose of subcutaneous infection produced chronic disease with significant (p<0.001) production of immune markers of infection like IFNγ, heat shock antigens (65, 71) and antibody titres against panel of M.tuberculosis antigens (ESAT-6, CFP-10, Ag85B, 45kDa, GroES, Hsp-16) all of which correlated with high bacterial burden in lungs and spleen. To conclude high dose of subcutaneous infection produces chronic TB infection in mice and can be used as convenient alternative to aerosol models in resource limited settings. Moreover assessment of immune markers namely mycobacterial antigens and antibodies can provide us valuable insights on modulation of immune response post infection. However further investigations along with optimization of study protocols are needed to justify the outcome of present study and establish such markers as surrogate endpoints of vaccine protection in preclinical and clinical studies in future.

show abstract

Section: Introductionmentioning

confidence: 99%

Investigation of Immune Biomarkers Using Subcutaneous Model of M. tuberculosis Infection in BALB/c Mice: A Preliminary Report

et al. 2015

View full text Add to dashboard Cite

show abstract

“…By increasing the dose of inoculation to induce more severe disease or by using more susceptible candidate strains, such as C3HeB/FeJ (Lanoix et al, 2015; Henao-Tamayo et al, 2015; Li et al, 2015), TNF-α or IFN-γ knockout mice (Ehlers et al, 2001; Manca et al, 2001; Turner and Orme, 2004; Green et al, 2013; Dorhoi et al, 2014; Francisco et al, 2015; Olleros et al, 2015), the onset of TB and evaluation process in mice could be accelerated above that of C57BL/6 or BALB/c. In addition, further applications of in vivo tracer techniques could facilitate detection of the abundance and distribution of the bacillus, as well as continuous monitoring of lesion progress in target organs; using these approaches could improve the accuracy of pre-clinical research, have higher detection sensitivity and safety, and optimize the use of laboratory animals (Sugawara et al, 2009; Kong and Cirillo, 2010; Kong et al, 2010, 2016; Zhang et al, 2010; Ozeki et al, 2015; Kato et al, 2016). …”

Section: Progress In Tb Animal Model Preparationmentioning

confidence: 99%

“…However, the current detection sensitivity is above 100 CFU, which is not sensitive enough to diagnose latent infection. The structure or features of fluorescent proteins should be modified to achieve a lower in vivo detection limit (Sugawara et al, 2009; Kong et al, 2010; Kong and Cirillo, 2010; Ozeki et al, 2015). …”

Section: Progress In Tb Animal Model Preparationmentioning

confidence: 99%

Animal Models for Tuberculosis in Translational and Precision Medicine

Tang

Sun

et al. 2017

Front. Microbiol.

View full text Add to dashboard Cite

Tuberculosis (TB) is a health threat to the global population. Anti-TB drugs and vaccines are key approaches for TB prevention and control. TB animal models are basic tools for developing biomarkers of diagnosis, drugs for therapy, vaccines for prevention and researching pathogenic mechanisms for identification of targets; thus, they serve as the cornerstone of comparative medicine, translational medicine, and precision medicine. In this review, we discuss the current use of TB animal models and their problems, as well as offering perspectives on the future of these models.

show abstract

“…Sugawara et al illustrated a new model, in which guinea pigs are infected by a subcutaneous route with 100-1000 CFU of M. tuberculosis H37Rv which expresses a green fluorescent protein (GFP). [31] In the next 10 months, a tuberculin skin test is performed on these mice to make sure their infection status. In this model, higher dose of inoculum (1000 CFU or more) is not apposite for developing the LTBI since these guinea pigs are prone to reactivation after 10 months.…”

Section: Guinea Pigmentioning

confidence: 99%

Models of Latent Tuberculosis: Their Salient Features, Limitations, and Development

2011

View full text Add to dashboard Cite

Latent tuberculosis is a subclinical condition caused by Mycobacterium tuberculosis, which affects about one-third of the population across the world. To abridge the chemotherapy of tuberculosis, it is necessary to have active drugs against latent form of M. tuberculosis. Therefore, it is imperative to devise in vitro and models of latent tuberculosis to explore potential drugs. In vitro models such as hypoxia, nutrient starvation, and multiple stresses are based on adverse conditions encountered by bacilli in granuloma. Bacilli experience oxygen depletion condition in hypoxia model, whereas the nutrient starvation model is based on deprivation of total nutrients from a culture medium. In the multiple stress model dormancy is induced by more than one type of stress. In silico mathematical models have also been developed to predict the interactions of bacilli with the host immune system and to propose structures for potential anti tuberculosis compounds. Besides these in vitro and in silico models, there are a number of in vivo animal models like mouse, guinea pig, rabbit, etc. Although they simulate human latent tuberculosis up to a certain extent but do not truly replicate human infection. All these models have their inherent merits and demerits. However, there is no perfect model for latent tuberculosis. Therefore, it is imperative to upgrade and refine existing models or develop a new model. However, battery of models will always be a better alternative to any single model as they will complement each other by overcoming their limitations.

show abstract

Establishment of A Guinea Pig Model of Latent Tuberculosis with GFP-introduced Mycobacterium Tuberculosis

Cited by 9 publications

References 19 publications

Investigation of Immune Biomarkers Using Subcutaneous Model of M. tuberculosis Infection in BALB/c Mice: A Preliminary Report

Investigation of Immune Biomarkers Using Subcutaneous Model of M. tuberculosis Infection in BALB/c Mice: A Preliminary Report

Animal Models for Tuberculosis in Translational and Precision Medicine

Models of Latent Tuberculosis: Their Salient Features, Limitations, and Development

Contact Info

Product

Resources

About