A recent study published in Immunology sheds new light on how the metabolism of T helper (Th) cells—critical components of our immune system—dictates their survival and function when exposed to ribosome-targeting antibiotics. The findings may have far-reaching implications for treating infections, autoimmune disorders, and even allergies.
Mitochondrial Translation: A Key Vulnerability
Mitochondria, often dubbed the powerhouses of cells, rely on their own protein synthesis machinery to maintain energy production. Antibiotics like chloramphenicol, which target bacterial ribosomes, can inadvertently impair mitochondrial translation due to structural similarities between bacterial and mitochondrial ribosomes. This study, led by researchers from the National Institute of Immunology in New Delhi, delves into how such mitochondrial translation disruption affects Th1 and Th2 cells—two distinct types of helper T cells with unique roles in immunity.
Dichotomy of Th1 and Th2 Cells
Th1 cells are the immune system’s frontline warriors, orchestrating responses against intracellular pathogens such as viruses. In contrast, Th2 cells coordinate defences against extracellular invaders like parasites and play a central role in allergic reactions.
The research revealed a striking dichotomy: while both Th1 and Th2 cells depend on oxidative phosphorylation (OXPHOS) for energy, their metabolic flexibility differs significantly. Th1 cells exhibited higher reliance on aerobic glycolysis—a rapid energy-generating process—making them less vulnerable to mitochondrial translation inhibition. Th2 cells, however, displayed a stronger dependence on OXPHOS, rendering them more susceptible to mitochondrial dysfunction.
Antibiotics and Immune Modulation
When treated with chloramphenicol, Th2 cells underwent apoptosis (programmed cell death) at a much higher rate than Th1 cells. This was linked to an upregulation of pro-apoptotic proteins Bim and Puma in Th2 cells. Surprisingly, Th1 cells showed resilience, likely due to their ability to switch metabolic gears and ramp up glycolysis when mitochondrial function was compromised.
Interestingly, the study also demonstrated that inhibiting glycolysis with 2-deoxyglucose (2-DG) had the opposite effect: Th1 cells were more sensitive to glycolytic disruption, while Th2 cells were comparatively resistant. These findings highlight the distinct metabolic wiring of these immune subsets and suggest that metabolic targeting could be used to selectively modulate immune responses.
Implications for Medicine
Antibiotics that interfere with mitochondrial translation could inadvertently modulate immune responses, potentially exacerbating or alleviating conditions such as allergies and autoimmune diseases where Th2 cells play a pathological role.
Furthermore, these insights pave the way for novel therapeutic strategies. By leveraging the metabolic dependencies of T cells, it may be possible to design interventions that selectively suppress or enhance specific immune pathways. This study underscores the importance of understanding the metabolic underpinnings of immune function. As antibiotics remain a cornerstone of modern medicine, their unintended effects on immune cells warrant careful consideration. By bridging the gap between metabolism and immunology, there is a possibility to fine-tune our immune system and improve health outcomes.
Reference:
Jawla, N., Kar, R., Patil, V. S., & Arimbasseri, G. A. (2025). Inherent metabolic preferences differentially regulate the sensitivity of Th1 and Th2 cells to ribosome-inhibiting antibiotics. Immunology, 174(1), 73–91. https://doi.org/10.1111/imm.13860