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

Abstract

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.

Visualization of the Macrophage's Dynamic in TB-HIV Co-Infection Using the Molecular Imaging Techniques: A Narrative Review

“…When HIV is co-infected, the likelihood of active tuberculosis disease is 15-21 times higher than when tuberculosis is the only infection and mycobacterium tuberculosis co-infection Health Dynamics is a major factor in mortality in HIV-infected people. (3,4) The epidemiology of these two illnesses may interact and be influenced by each other's causes. (5) According to Bell & Noursadeghi, (2017) HIV coinfection substantially increases the risk of developing active TB and conversely, TB co-infection will increase the rate of replication, spread, and genetic diversity of HIV-1.…”

Single-Cell Transcriptomics of Mtb/HIV Co-Infection

“…Though the primary function of granuloma is to contain the bacilli, in some instances, the bacilli can survive inside these structures for extended periods of time in a dormant state. Under immunosuppressive conditions, such as HIV co-infection, the bacilli escape the granuloma and spread to extrapulmonary organs causing the reactivation of LTBI [ 6 , 11 , 12 ]. Nonhuman primate (NHP) research has shown that there are direct cytopathic effects of Simian Immunodeficiency Virus (SIV) resulting in chronic immune activation, altered effector T cell phenotypes, and dysregulated T cell homeostasis that causes LTBI reactivation [ 13 ].…”