Abstract

Tuberculosis (TB) unfolds within a chemically reactive battlefield where host-derived reactive oxygen and nitrogen 
species (ROS/RNS) intersect with immune signaling to shape disease outcomes. While oxidative stress is essential 
for mycobacterial control, sustained redox imbalance damages host tissues, disrupts granuloma integrity, fuels 
inflammation, and may even enhance Mycobacterium tuberculosis (Mtb) persistence. This review synthesizes 
current understanding of redox–immune crosstalk in TB pathogenesis and critically evaluates antioxidant 
phytochemicals as host-directed therapy (HDT) candidates. We outline how key pathways-Nrf2/Keap1, NF-κB, 
HIF-1α, MAPK, and JAK/STAT-integrate redox signals to calibrate macrophage activation, autophagy, antigen 
presentation, and adaptive immunity. We then survey major phytochemical classes (polyphenols, terpenoids, 
organosulfur compounds, alkaloids) with reported effects on ROS/RNS homeostasis, inflammasome activity, 
mitochondrial function, and immunometabolism. Emerging data suggest that select compounds can (i) enhance 
bactericidal mechanisms without exacerbating tissue injury, (ii) temper pathological inflammation, (iii) promote 
autophagy and phagosome maturation, and (iv) mitigate anti-TB drug toxicities. We highlight formulation advances 
that improve bioavailability, summarize preclinical/early clinical signals, and discuss safety, pharmacokinetic, and 
drug–drug interaction considerations. Finally, we identify knowledge gaps and propose a translational roadmap for 
integrating rigorously characterized phytochemicals into TB HDT regimens.