Web of Science: 10 cites, Scopus: 19 cites, Google Scholar: cites,
Local Inflammation, Dissemination and Coalescence of Lesions Are Key for the Progression toward Active Tuberculosis: The Bubble Model
Prats Soler, Clara (Universitat Politècnica de Catalunya. Escola Superior d'Agricultura de Barcelona)
Vilaplana i Massaguer, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Valls, Joaquim (Universitat Politècnica de Catalunya. Escola Superior d'Agricultura de Barcelona)
Marzo Escartín, Elena (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Cardona, Pere-Joan (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
López, Daniel (Universitat Politècnica de Catalunya. Escola Superior d'Agricultura de Barcelona)

Data: 2016
Resum: The evolution of a tuberculosis (TB) infection toward active disease is driven by a combination of factors mostly related to the host response. The equilibrium between control of the bacillary load and the pathology generated is crucial as regards preventing the growth and proliferation of TB lesions. In addition, some experimental evidence suggests an important role of both local endogenous reinfection and the coalescence of neighboring lesions. Herein we propose a mathematical model that captures the essence of these factors by defining three hypotheses: (i) lesions grow logistically due to the inflammatory reaction; (ii) new lesions can appear as a result of extracellular bacilli or infected macrophages that escape from older lesions; and (iii) lesions can merge when they are close enough. This model was implemented in Matlab to simulate the dynamics of several lesions in a 3D space. It was also fitted to available microscopy data from infected C3HeB/FeJ mice, an animal model of active TB that reacts against Mycobacterium tuberculosis with an exaggerated inflammatory response. The results of the simulations show the dynamics observed experimentally, namely an initial increase in the number of lesions followed by fluctuations, and an exponential increase in the mean area of the lesions. In addition, further analysis of experimental and simulation results show a strong coincidence of the area distributions of lesions at day 21, thereby highlighting the consistency of the model. Three simulation series removing each one of the hypothesis corroborate their essential role in the dynamics observed. These results demonstrate that three local factors, namely an exaggerated inflammatory response, an endogenous reinfection, and a coalescence of lesions, are needed in order to progress toward active TB. The failure of one of these factors stops induction of the disease. This mathematical model may be used as a basis for developing strategies to stop the progression of infection toward disease in human lungs.
Ajuts: Instituto de Salud Carlos III FEDER/PI11/01702
Instituto de Salud Carlos III FEDER/PI14/01038
Nota: Altres ajuts: Miguel Servet CP13/00174
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: Article ; recerca ; Versió publicada
Matèria: Tuberculosi ; Mycobacterium tuberculosis ; Active tuberculosis ; Computational model ; Dynamic hypothesis ; Tuberculosis lesions in lungs
Publicat a: Frontiers in microbiology, Vol. 7 Núm. 33 (February 2016) , ISSN 1664-302X

DOI: 10.3389/fmicb.2016.00033
PMID: 26870005

11 p, 3.5 MB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Articles de recerca
Articles > Articles publicats

 Registre creat el 2017-05-18, darrera modificació el 2023-06-04

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