A reaction-diffusion model to understand granulomas formation inside secondary lobule during tuberculosis infection
Català, Martí (Institut Germans Trias i Pujol)
Prats, Clara (Institut Germans Trias i Pujol)
López, Daniel (Universitat Politècnica de Catalunya. Departament de Física)
Cardona, Pere-Joan (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Alonso Muñoz, Sergio (Universitat Politècnica de Catalunya. Departament de Física)

Data:	2020
Resum:	Mycobacterium tuberculosis (Mtb) is the causative agent for tuberculosis, the most extended infectious disease around the world. When Mtb enters inside the pulmonary alveolus it is rapidly phagocytosed by the alveolar macrophage. Although this controls the majority of inhaled microorganisms, in this case, Mtb survives inside the macrophage and multiplies. A posterior chemokine and cytokine cascade generated by the irruption of monocytes, neutrophils and posteriorly, by T-cells, does not necessarily stop the growth of the granuloma. Interestingly, the encapsulation process built by fibroblasts is able to surround the lesion and stop its growing. The success of this last process determines if the host enters in an asymptomatic latent state or continues into a life-threatening and infective active tuberculosis disease (TB). Understanding such dichotomic process is challenging, and computational modeling can bring new ideas. Thus, we have modeled the different stages of the infection, first in a single alveolus (a sac with a radius of 0. 15 millimeters) and, second, inside a secondary lobule (a compartment of the lungs of around 3 cm 3). We have employed stochastic reaction-diffusion equations to model the interactions among the cells and the diffusive transport to neighboring alveolus. The whole set of equations have successfully described the encapsulation process and determine that the size of the lesions depends on its position on the secondary lobule. We conclude that size and shape of the secondary lobule are the relevant variables to control the lesions, and, therefore, to avoid the evolution towards TB development. As lesions appear near to interlobular connective tissue they are easily controlled and their growth is drastically stopped, in this sense secondary lobules with a more flattened shape could control better the lesion.
Ajuts:	"la Caixa" Foundation LCF/PR/GN17/50300003 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR-500 Agencia Estatal de Investigación PGC2018-095456-B-I00
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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PloS one, Vol. 15 (september 2020) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0239289
PMID: 32936814

20 p, 2.1 MB

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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)
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