Immune cells rewire metabolic pathways (glycolysis, OXPHOS, FAO, and the TCA cycle) to meet functional demands. This immunometabolism shapes pathogen sensing, effector functions, resolution, and memory. In infectious disease, pathogens manipulate host metabolism; in ageing, inflammaging, mitochondrial dysfunction, and altered nutrient sensing blunt responses and reduce vaccine efficacy. Emerging work identifies metabolites as signaling nodes (itaconate, succinate, lactate; NAD⁺/redox) and regulators (mTOR, AMPK, HIF-1α) linking organelle quality control (mitophagy) to trained immunity, T-cell exhaustion, and B-cell maturation. Yet causal maps across tissues and life stages remain incomplete, and actionable biomarkers and targets are uneven.

This Research Topic seeks mechanistic, multi-omics, and interventional studies that define metabolic circuits in infection and ageing and test strategies to modulate them (e.g., metabolic adjuvants, NAD⁺ boosters, microbiome-derived metabolites, exercise/diet, and rational drug repurposing) to improve prevention, vaccine performance, and therapy.

This Research Topic targets a central gap: we lack causal, clinically actionable maps linking immune cell metabolism to host defense and vaccine performance across infectious diseases and ageing. Evidence shows that pathways such as glycolysis, OXPHOS, FAO and the TCA cycle, regulated by mTOR/AMPK/HIF-1α and shaped by metabolites (itaconate, succinate, lactate; NAD⁺/redox), tune innate and adaptive immunity. Yet cell-state, tissue, and life-course specificity remain poorly defined, and translation to biomarkers and interventions is uneven.

We aim to assemble mechanistic and translational studies that:
1. Define how ageing remodels immunometabolic circuits in infection
2. Identify biomarkers predicting susceptibility, severity, and vaccine response
3. Test strategies to modulate metabolism—metabolic adjuvants, NAD⁺ boosters, itaconate derivatives, glycolysis/FAO modulators, microbiome-derived metabolites, exercise and dietary interventions, or drug repurposing (e.g., metformin, rapamycin).

We encourage single-cell and multi-omics, isotope tracing, functional assays (e.g., Seahorse), causal perturbations, and well-phenotype human cohorts with longitudinal sampling. Harmonized methods and clear clinical endpoints are strongly encouraged.

The goal is a toolkit of targets, assays, and protocols that can improve prevention, vaccination, and therapy in older adults and across infections.

This Research Topic focuses on host immunometabolism in infectious disease and ageing. We welcome studies that define how metabolic pathways (glycolysis, OXPHOS, FAO, TCA cycle) and regulators (mTOR, AMPK, HIF-1α) shape innate and adaptive immunity, disease severity, and vaccine responses. Priority themes include:
- Metabolite signaling (itaconate, succinate, lactate; NAD⁺/redox)
- Mitochondrial dysfunction/mitophagy
- Trained immunity and T-cell exhaustion
- Biomarker discovery and risk stratification
- Microbiome–metabolite–immune axes; and interventions (metabolic adjuvants, NAD⁺ boosters, diet/exercise, microbiome-targeted strategies, rational drug repurposing).

We encourage mechanistic and translational work using single-cell/multi-omics, isotope tracing, functional bioenergetics (e.g., Seahorse), causal perturbations, robust animal models, and well-phenotyped human cohorts (including older adults) with clear clinical endpoints.

Manuscript types: Original Research, Brief Research Report, Methods/Protocols, Resource, Review, Mini-Review, Systematic Review/Meta-analysis, Hypothesis & Theory, Perspective/Opinion.
Articles without an immunological focus are out of scope for this journal.

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Immunometabolism in infectious disease and ageing