Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1784627109502648320 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8730292 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT ruggierostevem mathematicalmodelingoftuberculosisgranulomaactivation AT pilvankarminur mathematicalmodelingoftuberculosisgranulomaactivation AT fordversyptashleen mathematicalmodelingoftuberculosisgranulomaactivation |