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The Small Breathing Amplitude at the Upper Lobes Favors the Attraction of Polymorphonuclear Neutrophils to Mycobacterium tuberculosis Lesions and Helps to Understand the Evolution toward Active Disease in An Individual-Based Model
Cardona, Pere-Joan (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Prats Soler, Clara (Universitat Politècnica de Catalunya. Escola Superior d'Agricultura de Barcelona)

Fecha: 2016
Resumen: Infection with Mycobacterium tuberculosis (Mtb) can induce two kinds of lesions, namely proliferative and exudative. The former are based on the presence of macrophages with controlled induction of intragranulomatous necrosis, and are even able to stop its physical progression, thus avoiding the induction of active tuberculosis (TB). In contrast, the most significant characteristic of exudative lesions is their massive infiltration with polymorphonuclear neutrophils (PMNs), which favor enlargement of the lesions and extracellular growth of the bacilli. We have built an individual-based model (IBM) (known as "TBPATCH") using the NetLogo interface to better understand the progression from Mtb infection to TB. We have tested four main factors previously identified as being able to favor the infiltration of Mtb-infected lesions with PMNs, namely the tolerability of infected macrophages to the bacillary load; the capacity to modulate the Th17 response; the breathing amplitude (BAM) (large or small in the lower and upper lobes respectively), which influences bacillary drainage at the alveoli; and the encapsulation of Mtb-infected lesions by the interlobular septae that structure the pulmonary parenchyma into secondary lobes. Overall, although all the factors analyzed play some role, the small BAM is the major factor determining whether Mtb-infected lesions become exudative, and thus induce TB, thereby helping to understand why this usually takes place in the upper lobes. This information will be very useful for the design of future prophylactic and therapeutic approaches against TB.
Nota: Plan Nacional I+D+I; ISCIII-Subdirección General de Evaluación; i EU Regional Development Fund (FEDER)
Nota: Número d'acord de subvenció ISCIII/FEDER/PI11/01702
Nota: Número d'acord de subvenció ISCIII/FEDER/PI14/01038
Derechos: 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
Lengua: Anglès
Documento: article ; recerca ; publishedVersion
Materia: Individual-Based Model; NetLogo; Th17; alveolar macrophages tolerability; bacillary drainage; breathing amplitude; polymorphonuclear neutrophils; tuberculosis
Publicado en: Frontiers in microbiology, Vol. 7 Núm. 654 (March 2016) , ISSN 1664-302X

DOI: 10.3389/fmicb.2016.00354
PMID: 27065951

18 p, 9.9 MB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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 Registro creado el 2017-05-18, última modificación el 2020-08-09

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