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Systems biology approaches to investigate the role of granulomas in TB-HIV coinfection

The risk of active tuberculosis disease is 15-21 times higher in those coinfected with human immunodeficiency virus-1 (HIV) compared to tuberculosis alone, and tuberculosis is the leading cause of death in HIV+ individuals. Mechanisms driving synergy between Mycobacterium tuberculosis (Mtb) and HIV...

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Autores principales: Hoerter, Alexis, Arnett, Eusondia, Schlesinger, Larry S., Pienaar, Elsje
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9670175/
https://www.ncbi.nlm.nih.gov/pubmed/36405707
http://dx.doi.org/10.3389/fimmu.2022.1014515
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author Hoerter, Alexis
Arnett, Eusondia
Schlesinger, Larry S.
Pienaar, Elsje
author_facet Hoerter, Alexis
Arnett, Eusondia
Schlesinger, Larry S.
Pienaar, Elsje
author_sort Hoerter, Alexis
collection PubMed
description The risk of active tuberculosis disease is 15-21 times higher in those coinfected with human immunodeficiency virus-1 (HIV) compared to tuberculosis alone, and tuberculosis is the leading cause of death in HIV+ individuals. Mechanisms driving synergy between Mycobacterium tuberculosis (Mtb) and HIV during coinfection include: disruption of cytokine balances, impairment of innate and adaptive immune cell functionality, and Mtb-induced increase in HIV viral loads. Tuberculosis granulomas are the interface of host-pathogen interactions. Thus, granuloma-based research elucidating the role and relative impact of coinfection mechanisms within Mtb granulomas could inform cohesive treatments that target both pathogens simultaneously. We review known interactions between Mtb and HIV, and discuss how the structure, function and development of the granuloma microenvironment create a positive feedback loop favoring pathogen expansion and interaction. We also identify key outstanding questions and highlight how coupling computational modeling with in vitro and in vivo efforts could accelerate Mtb-HIV coinfection discoveries.
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spelling pubmed-96701752022-11-18 Systems biology approaches to investigate the role of granulomas in TB-HIV coinfection Hoerter, Alexis Arnett, Eusondia Schlesinger, Larry S. Pienaar, Elsje Front Immunol Immunology The risk of active tuberculosis disease is 15-21 times higher in those coinfected with human immunodeficiency virus-1 (HIV) compared to tuberculosis alone, and tuberculosis is the leading cause of death in HIV+ individuals. Mechanisms driving synergy between Mycobacterium tuberculosis (Mtb) and HIV during coinfection include: disruption of cytokine balances, impairment of innate and adaptive immune cell functionality, and Mtb-induced increase in HIV viral loads. Tuberculosis granulomas are the interface of host-pathogen interactions. Thus, granuloma-based research elucidating the role and relative impact of coinfection mechanisms within Mtb granulomas could inform cohesive treatments that target both pathogens simultaneously. We review known interactions between Mtb and HIV, and discuss how the structure, function and development of the granuloma microenvironment create a positive feedback loop favoring pathogen expansion and interaction. We also identify key outstanding questions and highlight how coupling computational modeling with in vitro and in vivo efforts could accelerate Mtb-HIV coinfection discoveries. Frontiers Media S.A. 2022-10-31 /pmc/articles/PMC9670175/ /pubmed/36405707 http://dx.doi.org/10.3389/fimmu.2022.1014515 Text en Copyright © 2022 Hoerter, Arnett, Schlesinger and Pienaar https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Hoerter, Alexis
Arnett, Eusondia
Schlesinger, Larry S.
Pienaar, Elsje
Systems biology approaches to investigate the role of granulomas in TB-HIV coinfection
title Systems biology approaches to investigate the role of granulomas in TB-HIV coinfection
title_full Systems biology approaches to investigate the role of granulomas in TB-HIV coinfection
title_fullStr Systems biology approaches to investigate the role of granulomas in TB-HIV coinfection
title_full_unstemmed Systems biology approaches to investigate the role of granulomas in TB-HIV coinfection
title_short Systems biology approaches to investigate the role of granulomas in TB-HIV coinfection
title_sort systems biology approaches to investigate the role of granulomas in tb-hiv coinfection
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9670175/
https://www.ncbi.nlm.nih.gov/pubmed/36405707
http://dx.doi.org/10.3389/fimmu.2022.1014515
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