Infectious diseases significantly influence metabolic processes within the host, playing a crucial role in the dynamics of host-pathogen interactions. Pathogens, ranging from Mycobacterium tuberculosis to SARS-CoV-2, strategically manipulate host metabolic systems—such as glycolytic modifications, mitochondrial activity, and lipid regulation—to escape immune detection and establish persistent infections. Recent advancements in immunometabolism and the use of cutting-edge technologies like single-cell sequencing and multi-omics integration have unveiled intricate intersections between metabolic and inflammatory pathways. These insights bring us closer to understanding the complexity of infection pathophysiology. However, a seamless transition from basic discoveries to clinical applications remains challenging, particularly considering factors such as comorbidities, drug resistance, and variable patient outcomes.

This Research Topic aims to address key questions in this field: How do pathogens alter host metabolic circuits through virulence factors across different cellular environments? In what ways do pre-existing metabolic conditions like diabetes or obesity impact infection severity and immune response efficacy? Can targeting specific metabolic pathways provide solutions to overcoming antibiotic resistance or T cell exhaustion during chronic infections? Answering these questions is essential for developing Host-Directed Therapies (HDTs) that can work alongside traditional antimicrobial methods, minimize tissue damage, and improve recovery outcomes in complex diseases such as tuberculosis, HIV co-infections, and sepsis.

The overarching goal of this Research Topic is to connect fundamental immunophysiology with translational and clinical research, translating mechanistic discoveries into practical therapeutic approaches. To gain a comprehensive understanding, we invite contributions exploring the metabolic determinants of infection outcomes at molecular, cellular, and organismal levels. Through a synergy of experimental models, clinical insights, and computational methodologies, this collection aspires to:

o Decipher pathogen-specific strategies to manipulate host metabolism, such as Mtb's suppression of HIF-1α in macrophages or viral control of AMPK/mTOR pathways.

o Identify metabolic factors contributing to immune dysfunction, including the failure of CD8+ T cell mitochondria during chronic Mtb infections and neutrophil glycolytic bursts in sepsis.

o Investigate how comorbidities, like diabetes or obesity, interact with infections to influence metabolic responses.

o Evaluate the potential of metabolically-targeted HDTs, such as the rejuvenation of T cell immunity with metformin or the use of ferroptosis/cuproptosis modulators for pathogen control.

We welcome submissions in the following areas, while not limited to them:

o Pathogen-specific adaptations in host metabolism: Mechanisms such as nutrient scavenging, redox balance strategies, and organelle remodeling.

o Metabolic checkpoints in immune cell fate, including glycolysis and oxidative phosphorylation shifts in macrophage polarization.

o The impact of comorbidities like diabetes, obesity, or aging on immunometabolic responses during infections.

o Innovations in therapy, targeting metabolites with small molecules or nanotherapeutics, and exploring metabolomic biomarkers for treatment efficacy prediction.

o Insights from evolutionary and ecological perspectives, focusing on metabolic trade-offs and environmental factors in infection susceptibility.

Submissions of all relevant article types are encouraged.

Are you interested in contributing a manuscript to this Research Topic?

Metabolic Pathways in Host-Pathogen Interactions: From Immune Response to Therapeutic Implications