Metabolomics as a Tool to Investigate HIV/TB Co-Infection

Abstract

The HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) and tuberculosis (TB) pandemics are perpetuated by a significant global burden of HIV/TB co-infection. The synergy between HIV and Mycobacterium tuberculosis (Mtb) during co-infection of a host is well established. While this synergy is known to be driven by immunological deterioration, the metabolic mechanisms thereof remain poorly understood. Metabolomics has been applied to study various aspects of HIV and Mtb infection separately, yielding insights into infection- and treatment-induced metabolic adaptations experienced by the host. Despite the contributions that metabolomics has made to the field, this approach has not yet been systematically applied to characterize the HIV/TB co-infected state. Considering that limited HIV/TB co-infection metabolomics studies have been published to date, this review briefly summarizes what is known regarding the HIV/TB co-infection synergism from a conventional and metabolomics perspective. It then explores metabolomics as a tool for the improved characterization of HIV/TB co-infection in the context of previously published human-related HIV infection and TB investigations, respectively as well as for addressing the gaps in existing knowledge based on the similarities and deviating trends reported in these HIV infection and TB studies.

HIV-Differentiated Metabolite N-Acetyl-L-Alanine Dysregulates Human Natural Killer Cell Responses to Mycobacterium tuberculosis Infection

“…Metabolomics provides a versatile tool to study the host immune responses to pathogen infections because metabolism offers a source of energy required for immune cell function. During HIV and Mtb infection/co-infection, immune cell activation and inflammation have also been shown to correlate with metabolic changes in the immune cells [ 38 , 39 , 40 , 41 ]. However, the mechanisms of how specific metabolites affect the immune responses to HIV/ Mtb infections remain elusive.…”

“…Amino acids participate in energy production during cell metabolism, and some amino acids are involved in oxidative stress and redox signaling during HIV and Mtb infection [ 38 , 39 ]. These physiological activities are tightly coupled with immune activation, as revealed by a previous study indicating that alanine is essential for CD4+ T-cell activation [ 44 ].…”

HIV-differentiated metabolite N-Acetyl-L-Alanine dysregulates human natural killer cell responses toMycobacterium tuberculosisinfection

“…Amino acids participate in energy production during cell metabolism, and some amino acids are involved in oxidative stress and redox signaling during HIV and Mtb infection[39, 40]. These physiological activities are tightly coupled with immune activation, as evidenced by the study of alanine is essential for CD4+ T cell activation[45].…”

Biomarker discovery for tuberculosis using metabolomics

“…These reviews have different focuses, with each one covering part of the studies in the literature. While some covered relatively broad aspects of TB research ( Goletti et al, 2016 ; Goletti et al, 2018 ; Kumar et al, 2017 ; du Preez et al, 2019 ; Kontsevaya et al, 2021 ), others addressed more focused topics, such as diagnostic biomarker ( Haas et al, 2016 ; du Preez et al, 2017 ), treatment monitoring ( Luies et al, 2017a ; Pitaloka et al, 2022 ), drug discovery ( Jansen and Rhee, 2017 ; Tuyiringire et al, 2018 ; Goff et al, 2020 ; Xu and Borah, 2022 ), mechanism of action of drugs ( Awasthi and Freundlich, 2017 ; Yuan et al, 2021 ) or anti-TB compounds ( Sakallioglu et al, 2021 ), drug resistance of Mtb and drug toxicty ( Combrink et al, 2020 ), as well as HIV/TB co-infection ( Liebenberg et al, 2021 ). Besides pulmonary TB, there are reviews on the status of metabolomics studies on tuberculosis meningitis as well ( Zhang et al, 2018 ; Isaiah et al, 2020 ; Huynh et al, 2022 ).…”