AUTHOR=Hoerter Alexis , Arnett Eusondia , Schlesinger Larry S. , Pienaar Elsje 

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

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1014515

DOI=10.3389/fimmu.2022.1014515

ISSN=1664-3224

ABSTRACT=<p>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 <italic>Mycobacterium tuberculosis</italic> (<italic>Mtb</italic>) and HIV during coinfection include: disruption of cytokine balances, impairment of innate and adaptive immune cell functionality, and <italic>Mtb</italic>-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 <italic>Mtb</italic> granulomas could inform cohesive treatments that target both pathogens simultaneously. We review known interactions between <italic>Mtb</italic> 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 <italic>in vitro</italic> and <italic>in vivo</italic> efforts could accelerate <italic>Mtb</italic>-HIV coinfection discoveries.</p>