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Mathematical Modeling of Tuberculosis Granuloma Activation

Tuberculosis (TB) is one of the most common infectious diseases worldwide. It is estimated that one-third of the world’s population is infected with TB. Most have the latent stage of the disease that can later transition to active TB disease. TB is spread by aerosol droplets containing Mycobacterium...

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Autores principales: Ruggiero, Steve M., Pilvankar, Minu R., Ford Versypt, Ashlee N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8730292/
https://www.ncbi.nlm.nih.gov/pubmed/34993126
http://dx.doi.org/10.3390/pr5040079
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author Ruggiero, Steve M.
Pilvankar, Minu R.
Ford Versypt, Ashlee N.
author_facet Ruggiero, Steve M.
Pilvankar, Minu R.
Ford Versypt, Ashlee N.
author_sort Ruggiero, Steve M.
collection PubMed
description Tuberculosis (TB) is one of the most common infectious diseases worldwide. It is estimated that one-third of the world’s population is infected with TB. Most have the latent stage of the disease that can later transition to active TB disease. TB is spread by aerosol droplets containing Mycobacterium tuberculosis (Mtb). Mtb bacteria enter through the respiratory system and are attacked by the immune system in the lungs. The bacteria are clustered and contained by macrophages into cellular aggregates called granulomas. These granulomas can hold the bacteria dormant for long periods of time in latent TB. The bacteria can be perturbed from latency to active TB disease in a process called granuloma activation when the granulomas are compromised by other immune response events in a host, such as HIV, cancer, or aging. Dysregulation of matrix metalloproteinase 1 (MMP-1) has been recently implicated in granuloma activation through experimental studies, but the mechanism is not well understood. Animal and human studies currently cannot probe the dynamics of activation, so a computational model is developed to fill this gap. This dynamic mathematical model focuses specifically on the latent to active transition after the initial immune response has successfully formed a granuloma. Bacterial leakage from latent granulomas is successfully simulated in response to the MMP-1 dynamics under several scenarios for granuloma activation.
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spelling pubmed-87302922022-01-05 Mathematical Modeling of Tuberculosis Granuloma Activation Ruggiero, Steve M. Pilvankar, Minu R. Ford Versypt, Ashlee N. Processes (Basel) Article Tuberculosis (TB) is one of the most common infectious diseases worldwide. It is estimated that one-third of the world’s population is infected with TB. Most have the latent stage of the disease that can later transition to active TB disease. TB is spread by aerosol droplets containing Mycobacterium tuberculosis (Mtb). Mtb bacteria enter through the respiratory system and are attacked by the immune system in the lungs. The bacteria are clustered and contained by macrophages into cellular aggregates called granulomas. These granulomas can hold the bacteria dormant for long periods of time in latent TB. The bacteria can be perturbed from latency to active TB disease in a process called granuloma activation when the granulomas are compromised by other immune response events in a host, such as HIV, cancer, or aging. Dysregulation of matrix metalloproteinase 1 (MMP-1) has been recently implicated in granuloma activation through experimental studies, but the mechanism is not well understood. Animal and human studies currently cannot probe the dynamics of activation, so a computational model is developed to fill this gap. This dynamic mathematical model focuses specifically on the latent to active transition after the initial immune response has successfully formed a granuloma. Bacterial leakage from latent granulomas is successfully simulated in response to the MMP-1 dynamics under several scenarios for granuloma activation. 2017-12-11 2017-12 /pmc/articles/PMC8730292/ /pubmed/34993126 http://dx.doi.org/10.3390/pr5040079 Text en https://creativecommons.org/licenses/by/4.0/This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Ruggiero, Steve M.
Pilvankar, Minu R.
Ford Versypt, Ashlee N.
Mathematical Modeling of Tuberculosis Granuloma Activation
title Mathematical Modeling of Tuberculosis Granuloma Activation
title_full Mathematical Modeling of Tuberculosis Granuloma Activation
title_fullStr Mathematical Modeling of Tuberculosis Granuloma Activation
title_full_unstemmed Mathematical Modeling of Tuberculosis Granuloma Activation
title_short Mathematical Modeling of Tuberculosis Granuloma Activation
title_sort mathematical modeling of tuberculosis granuloma activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8730292/
https://www.ncbi.nlm.nih.gov/pubmed/34993126
http://dx.doi.org/10.3390/pr5040079
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