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 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.

Automated summary

Coinfection with HIV and tuberculosis increases the risk of active tuberculosis and is the leading cause of death in HIV positive individuals. Tuberculosis granulomas, the sites of host-pathogen interactions, play a crucial role in understanding and treating coinfection. Coupling computational modeling with in vitro and in vivo experiments can accelerate discoveries in Mtb-HIV coinfection.